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  <TITLE>S-8</TITLE>
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   <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>As filed with the Securities and Exchange Commission on March 11, 2025 </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="right"><B><FONT STYLE="white-space:nowrap">Registration&nbsp;No.&nbsp;333-&#8195;&#8195;&#8195;</FONT> </B></P>
  <P STYLE="font-size:4pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P> <P STYLE="line-height:1.0pt;margin-top:0pt;margin-bottom:0pt;border-bottom:1px solid #000000">&nbsp;</P>
  <P STYLE="line-height:3.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1px solid #000000">&nbsp;</P> <P STYLE="margin-top:4pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>UNITED STATES </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>SECURITIES AND EXCHANGE COMMISSION </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:12pt; font-family:Times New Roman" ALIGN="center"><B>Washington, D.C. 20549 </B></P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center>
  <P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center> <P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B><FONT
  STYLE="white-space:nowrap">FORM&nbsp;S-8</FONT> </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>REGISTRATION STATEMENT </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:12pt; font-family:Times New Roman" ALIGN="center"><B><I>UNDER </I></B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:12pt; font-family:Times New Roman" ALIGN="center"><B><I>THE
  SECURITIES ACT OF 1933 </I></B></P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center> <P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center>
  <P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:24pt; font-family:Times New Roman" ALIGN="center"><B>Xilio Therapeutics,&nbsp;Inc. </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>(Exact Name of Registrant as Specified in Its Charter) </B></P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center>
  <P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
  <TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="100%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:8pt" ALIGN="center">
  
  
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  <TD VALIGN="top" ALIGN="center"><B>Delaware</B></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"><B><FONT STYLE="white-space:nowrap">85-1623397</FONT></B></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:8pt">
  <TD VALIGN="top" ALIGN="center"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(State or Other Jurisdiction of</B></P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>Incorporation or Organization)</B></P></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(I.R.S. Employer</B></P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>Identification No.)</B></P></TD></TR>
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  <TD VALIGN="top" ALIGN="center"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>828 Winter Street, Suite&nbsp;300</B></P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Waltham, Massachusetts</B></P></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom" ALIGN="center"><B>02451</B></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:8pt">
  <TD VALIGN="top" ALIGN="center"><B>(Address of Principal Executive Offices)</B></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"><B>(Zip Code)</B></TD></TR>
  </TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>2021 Stock Incentive Plan </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>2021 Employee Stock Purchase Plan </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Amended and Restated 2022 Inducement Stock Incentive Plan </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(Full Title of the Plan) </B></P>
  <P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Ren&eacute; Russo </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>President and Chief Executive Officer </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Xilio Therapeutics,&nbsp;Inc. </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>828 Winter Street, Suite&nbsp;300 </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Waltham, Massachusetts 02451 </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(Name and Address of Agent for Service) </B></P>
  <P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>(857) <FONT STYLE="white-space:nowrap">524-2466</FONT> </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(Telephone Number, Including Area Code, of Agent for Service) </B></P>
  <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center> <P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center>
  <P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B><I>Copy to: </I></B></P> <P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Caroline
  Hensley </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Chief Legal Officer </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Xilio Therapeutics,&nbsp;Inc. </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>828 Winter Street, Suite&nbsp;300 </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Waltham, Massachusetts 02451 </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>(857) <FONT STYLE="white-space:nowrap">524-2466</FONT> </B></P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center>
  <P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center> <P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Indicate by check mark whether
  the registrant is a large accelerated filer, an accelerated filer, <FONT STYLE="white-space:nowrap">a&nbsp;non-accelerated&nbsp;filer,</FONT> a smaller reporting company, or an emerging growth company. See the definitions of &#147;large accelerated
  filer,&#148; &#147;accelerated filer,&#148; &#147;smaller reporting company,&#148; and &#147;emerging growth company&#148; in <FONT STYLE="white-space:nowrap">Rule&nbsp;12b-2&nbsp;of</FONT> the Exchange Act. </P>
  <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
  <TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="100%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" ALIGN="center">
  
  
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  <TD WIDTH="57%"></TD>
  
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  <TD WIDTH="21%"></TD>
  
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  <TD VALIGN="bottom">Large&nbsp;accelerated&nbsp;filer</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom">&#9744;</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="bottom">Accelerated&nbsp;filer</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom">&#9744;</TD></TR>
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  <TD HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="bottom">Non-accelerated filer</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom">&#9746;</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="bottom">Smaller&nbsp;reporting&nbsp;company</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom">&#9746;</TD></TR>
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  <TD VALIGN="bottom"></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
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  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="bottom">Emerging&nbsp;growth&nbsp;company</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom">&#9746;</TD></TR>
  </TABLE> <P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period
  for complying with any new or revised financial accounting standards provided pursuant to Section&nbsp;7(a)(2)(B)&nbsp;of the Securities Act.&#8194;&#9744; </P> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
  <P STYLE="line-height:1.0pt;margin-top:0pt;margin-bottom:0pt;border-bottom:1px solid #000000">&nbsp;</P> <P STYLE="line-height:3.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1px solid #000000">&nbsp;</P>
  </DIV></Center>
  
  
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  <HR SIZE="3" style="COLOR:#999999" WIDTH="100%" ALIGN="CENTER">
  
  
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   <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Statement of Incorporation by Reference </B></P>
  <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">This Registration Statement on Form <FONT STYLE="white-space:nowrap">S-8,</FONT> relating to the 2021 Stock Incentive Plan (the &#147;2021 Plan&#148;), the
  2021 Employee Stock Purchase Plan (the &#147;2021 ESPP&#148;), and the Amended and Restated 2022 Inducement Stock Incentive Plan (the &#147;2022 Inducement Plan&#148;) of Xilio Therapeutics, Inc. (the &#147;Registrant&#148;), is being filed for the
  purpose of registering additional securities of the same class as other securities for which a Registration Statement on Form <FONT STYLE="white-space:nowrap">S-8</FONT> has previously been filed and is effective. Accordingly, this Registration
  Statement incorporates by reference the contents of (i)&nbsp;the Registration Statement on Form <FONT STYLE="white-space:nowrap">S-8</FONT> (File <FONT STYLE="white-space:nowrap">No.&nbsp;333-260460)</FONT> filed with the Securities and Exchange
  Commission (&#147;SEC&#148;) on <A HREF="http://www.sec.gov/Archives/edgar/data/1840233/000110465921129142/tm2115750d22_s8.htm">October<U></U>&nbsp;25, 2021</A> by the Registrant relating to the 2021 Plan and the 2021 ESPP, (ii)&nbsp;the
  Registration Statement on Form <FONT STYLE="white-space:nowrap">S-8</FONT> (File <FONT STYLE="white-space:nowrap">No.&nbsp;
  333-263178)</FONT> filed with the SEC on <A HREF="http://www.sec.gov/Archives/edgar/data/1840233/000155837022002619/tmb-20220301xs8.htm">March<U></U>&nbsp;1, 2022</A> by the Registrant relating to the 2021 Plan and the 2021 ESPP, (iii)&nbsp;the
  Registration Statement on Form <FONT STYLE="white-space:nowrap">S-8</FONT> (File <FONT STYLE="white-space:nowrap">No.&nbsp;
  333-270240)</FONT> filed with the SEC on <A HREF="http://www.sec.gov/Archives/edgar/data/1840233/000155837023002701/tmb-20230302xs8.htm">March<U></U>&nbsp;2, 2023</A> by the Registrant relating to the 2021 Plan, the 2021 ESPP, and the 2022 Inducement
  Plan, and (iv)&nbsp;the Registration Statement on Form <FONT STYLE="white-space:nowrap">S-8</FONT> (File <FONT STYLE="white-space:nowrap">No.&nbsp;
  333-278427)</FONT> filed with the SEC on <A HREF="http://www.sec.gov/Archives/edgar/data/1840233/000155837024004537/tmb-20240401xs8.htm">April<U></U>&nbsp;1, 2024</A> by the Registrant relating to the 2021 Plan and the 2021 ESPP, except, in each
  case, to the extent amended or superseded by the contents hereof and for &#147;Item 8. Exhibits&#148; with respect to which the exhibit index set forth below is incorporated herein by reference. </P>
  <P STYLE="font-size:18pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
  <TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
  <TR style = "page-break-inside:avoid">
  <TD WIDTH="10%" VALIGN="top" ALIGN="left"><B>Item&#8201;8.</B></TD>
  <TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><B>Exhibits. </B></P></TD></TR></TABLE>
  <P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">The following exhibits are incorporated herein by reference: </P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
  <TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="100%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" ALIGN="center">
  
  
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  <TD WIDTH="92%"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:8pt">
  <TD VALIGN="bottom" NOWRAP ALIGN="center" STYLE="border-bottom:1.00pt solid #000000">Number</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="bottom" ALIGN="center" STYLE="border-bottom:1.00pt solid #000000"> <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:8pt; font-family:Times New Roman" ALIGN="center">Description</P></TD></TR>
  
  
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>4.1</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1840233/000110465921129996/tm2115750d23_ex3-1.htm">Restated Certificate of Incorporation of the Registrant (incorporated by reference to Exhibit<U></U>&nbsp;
  3.1 of the Company&#146;s Current Report on Form<U></U><FONT STYLE="white-space:nowrap">&nbsp;8-K</FONT> (File No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;
  001-40925),</FONT> filed with the Securities and Exchange Commission on October<U></U>&nbsp;26, 2021)</A></TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>4.2</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1840233/000155837023005393/xlo-20230328xex3d1.htm">Second Amended and Restated Bylaws of the Registrant (incorporated by reference to Exhibit<U></U>&nbsp;
  3.1 of the Company&#146;s Current Report on Form<U></U><FONT STYLE="white-space:nowrap">&nbsp;8-K</FONT> (File No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;001-40925),</FONT> filed with the Securities and Exchange Commission on April<U></U>&nbsp;
  3, 2023)</A></TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>5.1*</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="d934115dex51.htm">Opinion of Wilmer Cutler Pickering Hale and Dorr LLP, counsel to the Registrant </A></TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>23.1*</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="d934115dex231.htm">Consent of Ernst&nbsp;&amp; Young LLP, independent registered public accounting firm </A></TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>23.2*</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="d934115dex51.htm">Consent of Wilmer Cutler Pickering Hale and Dorr LLP (included in Exhibit&nbsp;5.1) </A></TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>24.1*</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="#sig">Power of attorney (included on the signature pages&nbsp;of this registration statement) </A></TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>99.1</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1840233/000110465921126920/tm2115750d13_ex10-5.htm">2021 Stock Incentive Plan (incorporated by reference to Exhibit<U></U>&nbsp;
  10.5 to the Registrant&#146;s Registration Statement on Form<U></U><FONT STYLE="white-space:nowrap">&nbsp;S-1</FONT><U></U>&nbsp;(File<U></U>&nbsp;No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;333-259973)</FONT><U></U>&nbsp;
  filed with the Securities and Exchange Commission on October<U></U>&nbsp;18, 2021)</A></TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>99.2</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1840233/000110465921126920/tm2115750d13_ex10-8.htm">2021 Employee Stock Purchase Plan (incorporated by reference to Exhibit<U></U>&nbsp;
  10.8 to the Registrant&#146;s Registration Statement on Form<U></U><FONT STYLE="white-space:nowrap">&nbsp;S-1</FONT><U></U>&nbsp;(File<U></U>&nbsp;No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;333-259973)</FONT><U></U>&nbsp;
  filed with the Securities and Exchange Commission on October<U></U>&nbsp;18, 2021)</A></TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>99.3</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1840233/000155837025002640/xlo-20241231xex10d9.htm">Amended and Restated 2022 Inducement Stock Incentive Plan (incorporated by reference to Exhibit&nbsp;
  10.9 to the Registrant&#146;s Annual Report on Form <FONT STYLE="white-space:nowrap">10-K</FONT> <FONT STYLE="white-space:nowrap">(File&nbsp;No.&nbsp;001-40925)&nbsp;filed</FONT> with the Securities and Exchange Commission on March&nbsp;11,
  2025)</A></TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>107*</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="d934115dexfilingfees.htm">Filing Fee Table </A></TD></TR>
  </TABLE> <P STYLE="line-height:8.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1px solid #000000;width:11%">&nbsp;</P>
  <TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
  <TR style = "page-break-inside:avoid">
  <TD WIDTH="4%" VALIGN="top" ALIGN="left">*</TD>
  <TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left">Filed herewith </P></TD></TR></TABLE>
  </DIV></Center>
  
  
  <p style="margin-top:1em; margin-bottom:0em; page-break-before:always"> </p>
  <HR SIZE="3" style="COLOR:#999999" WIDTH="100%" ALIGN="CENTER">
  
  
  <Center><DIV STYLE="width:8.5in" align="left">
   <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>SIGNATURES </B></P>
  <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Pursuant to the requirements of the Securities Act of 1933, as amended, the registrant certifies that it has reasonable grounds to believe that it meets all
  of the requirements for filing on <FONT STYLE="white-space:nowrap">Form&nbsp;S-8&nbsp;and</FONT> has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Waltham,
  Commonwealth of Massachusetts on this 11th day of March, 2025. </P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><DIV ALIGN="right">
  <TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="40%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt">
  
  
  <TR>
  
  <TD WIDTH="7%"></TD>
  
  <TD VALIGN="bottom" WIDTH="1%"></TD>
  <TD WIDTH="92%"></TD></TR>
  
  
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" COLSPAN="3"><B>XILIO THERAPEUTICS,&nbsp;INC.</B></TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top">By:</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:1pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Ren&eacute; Russo</P></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top"></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top">Ren&eacute; Russo</TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top"></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top">President and Chief Executive Officer</TD></TR>
  </TABLE></DIV>
  </DIV></Center>
  
  
  <p style="margin-top:1em; margin-bottom:0em; page-break-before:always"> </p>
  <HR SIZE="3" style="COLOR:#999999" WIDTH="100%" ALIGN="CENTER">
  
  
  <Center><DIV STYLE="width:8.5in" align="left">
   <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B><A NAME="sig"></A>POWER OF ATTORNEY AND SIGNATURES </B></P>
  <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">We, the undersigned officers and directors of Xilio Therapeutics,&nbsp;Inc., hereby severally constitute and appoint Ren&eacute; Russo and Caroline Hensley,
  and each of them singly (with full power to each of them to act alone), our true and lawful attorneys with full power of substitution and resubstitution in each of them for him and in his name, place and stead, and in any and all capacities, to sign
  for us and in our names in the capacities indicated below, the registration statement on <FONT STYLE="white-space:nowrap">Form&nbsp;S-8&nbsp;filed</FONT> herewith and any and all subsequent amendments to said registration statement, and generally to
  do all such things in our names and on our behalf in our capacities as officers and directors to enable Xilio Therapeutics,&nbsp;Inc. to comply with the provisions of the Securities Act of 1933, as amended, and all requirements of the Securities and
  Exchange Commission, hereby ratifying and confirming our signatures as they may be signed by our said attorneys, or any of them, to said registration statement and any and all amendments thereto. </P>
  <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Pursuant to the requirements of the Securities Act of 1933, as amended, this registration statement has been signed by the following persons in the capacities
  and on the dates indicated. </P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
  <TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="100%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" ALIGN="center">
  
  
  <TR>
  
  <TD WIDTH="33%"></TD>
  
  <TD VALIGN="bottom" WIDTH="1%"></TD>
  <TD WIDTH="39%"></TD>
  
  <TD VALIGN="bottom" WIDTH="1%"></TD>
  <TD WIDTH="26%"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:8pt">
  <TD VALIGN="bottom" NOWRAP ALIGN="center" STYLE="border-bottom:1.00pt solid #000000"> <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>Signature</B></P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="bottom" ALIGN="center" STYLE="border-bottom:1.00pt solid #000000"> <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>Title</B></P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="bottom" ALIGN="center" STYLE="border-bottom:1.00pt solid #000000"> <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>Date</B></P></TD></TR>
  
  
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Ren&eacute; Russo</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Ren&eacute; Russo</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">President and Chief Executive Officer, Director</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman"><I>(Principal Executive Officer)</I></P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center">March&nbsp;11, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Christopher Frankenfield</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Christopher Frankenfield</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Chief Financial Officer and Chief Operating Officer</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman"><I>(Principal Financial Officer)</I></P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center">March&nbsp;11, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Kevin Brennan</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Kevin Brennan</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Senior Vice President, Finance and Accounting</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman"><I>(Principal Accounting Officer)</I></P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center">March&nbsp;11, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Paul J. Clancy</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Paul J. Clancy</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top">Chair of the Board of Directors</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center">March&nbsp;11, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Sara M. Bonstein</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Sara M. Bonstein</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top">Director</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center">March&nbsp;11, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Aoife Brennan</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Aoife Brennan</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top">Director</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center">March&nbsp;11, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Daniel Curran</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Daniel Curran</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top">Director</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center">March&nbsp;11, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Robert Ross</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Robert Ross</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top">Director</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center">March&nbsp;11, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Christina Rossi</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Christina Rossi</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top">Director</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center">March&nbsp;11, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ James Shannon</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">James Shannon</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top">Director</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center">March&nbsp;11, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD>
  <TD HEIGHT="16" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Yuan Xu</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Yuan Xu</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top">Director</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center">March&nbsp;11, 2025</TD></TR>
  </TABLE>
  </DIV></Center>
  
  </BODY></HTML>
metadata_documents: [{"type": "S-8", "sequence": "1", "filename": "d934115ds8.htm", "description": "S-8", "secsgml_size_bytes": 34975}]
metadata_filer: {"company-data": {"conformed-name": "Xilio Therapeutics, Inc.", "cik": "0001840233", "assigned-sic": "2834", "organization-name": "03 Life Sciences", "irs-number": "851623397", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-285701", "film-number": "25725975"}, "business-address": {"street1": "828 WINTER STREET", "city": "WALTHAM", "state": "MA", "zip": "02451", "phone": "617-833-1027"}, "mail-address": {"street1": "828 WINTER STREET", "city": "WALTHAM", "state": "MA", "zip": "02451"}}
text: S-8
  As filed with the Securities and Exchange Commission on March 11, 2025
  Registration No. 333-
  UNITED STATES
  SECURITIES AND EXCHANGE COMMISSION
  Washington, D.C. 20549
  FORM S-8
  REGISTRATION STATEMENT
  UNDER
  THE
  SECURITIES ACT OF 1933
  Xilio Therapeutics, Inc.
  (Exact Name of Registrant as Specified in Its Charter)
  Delaware
  85-1623397
  (State or Other Jurisdiction of
  Incorporation or Organization)
  (I.R.S. Employer
  Identification No.)
  828 Winter Street, Suite 300
  Waltham, Massachusetts
  02451
  (Address of Principal Executive Offices)
  (Zip Code)
  2021 Stock Incentive Plan
  2021 Employee Stock Purchase Plan
  Amended and Restated 2022 Inducement Stock Incentive Plan
  (Full Title of the Plan)
  René Russo
  President and Chief Executive Officer
  Xilio Therapeutics, Inc.
  828 Winter Street, Suite 300
  Waltham, Massachusetts 02451
  (Name and Address of Agent for Service)
  (857)
  524-2466
  (Telephone Number, Including Area Code, of Agent for Service)
  Copy to:
  Caroline
  Hensley
  Chief Legal Officer
  Xilio Therapeutics, Inc.
  828 Winter Street, Suite 300
  Waltham, Massachusetts 02451
  (857)
  524-2466
  Indicate by check mark whether
  the registrant is a large accelerated filer, an accelerated filer,
  a non-accelerated filer,
  a smaller reporting company, or an emerging growth company. See the definitions of "large accelerated
  filer," "accelerated filer," "smaller reporting company," and "emerging growth company" in
  Rule 12b-2 of
  the Exchange Act.
  Large accelerated filer
  ☐
  Accelerated filer
  ☐
  Non-accelerated filer
  ☒
  Smaller reporting company
  ☒
  Emerging growth company
  ☒
  If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period
  for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☐
  Statement of Incorporation by Reference
  This Registration Statement on Form
  S-8,
  relating to the 2021 Stock Incentive Plan (the "2021 Plan"), the
  2021 Employee Stock Purchase Plan (the "2021 ESPP"), and the Amended and Restated 2022 Inducement Stock Incentive Plan (the "2022 Inducement Plan") of Xilio Therapeutics, Inc. (the "Registrant"), is being filed for the
  purpose of registering additional securities of the same class as other securities for which a Registration Statement on Form
  S-8
  has previously been filed and is effective. Accordingly, this Registration
  Statement incorporates by reference the contents of (i) the Registration Statement on Form
  S-8
  (File
  No. 333-260460)
  filed with the Securities and Exchange
  Commission ("SEC") on
  October
  25, 2021
  by the Registrant relating to the 2021 Plan and the 2021 ESPP, (ii) the
  Registration Statement on Form
  S-8
  (File
  No. 
  333-263178)
  filed with the SEC on
  March
  1, 2022
  by the Registrant relating to the 2021 Plan and the 2021 ESPP, (iii) the
  Registration Statement on Form
  S-8
  (File
  No. 
  333-270240)
  filed with the SEC on
  March
  2, 2023
  by the Registrant relating to the 2021 Plan, the 2021 ESPP, and the 2022 Inducement
  Plan, and (iv) the Registration Statement on Form
  S-8
  (File
  No. 
  333-278427)
  filed with the SEC on
  April
  1, 2024
  by the Registrant relating to the 2021 Plan and the 2021 ESPP, except, in each
  case, to the extent amended or superseded by the contents hereof and for "Item 8. Exhibits" with respect to which the exhibit index set forth below is incorporated herein by reference.
  Item 8.
  Exhibits.
  The following exhibits are incorporated herein by reference:
  Number
  Description
  4.1
  Restated Certificate of Incorporation of the Registrant (incorporated by reference to Exhibit
  3.1 of the Company's Current Report on Form
  8-K
  (File No.
  001-40925),
  filed with the Securities and Exchange Commission on October
  26, 2021)
  4.2
  Second Amended and Restated Bylaws of the Registrant (incorporated by reference to Exhibit
  3.1 of the Company's Current Report on Form
  8-K
  (File No.
  001-40925),
  filed with the Securities and Exchange Commission on April
  3, 2023)
  5.1*
  Opinion of Wilmer Cutler Pickering Hale and Dorr LLP, counsel to the Registrant
  23.1*
  Consent of Ernst & Young LLP, independent registered public accounting firm
  23.2*
  Consent of Wilmer Cutler Pickering Hale and Dorr LLP (included in Exhibit 5.1)
  24.1*
  Power of attorney (included on the signature pages of this registration statement)
  99.1
  2021 Stock Incentive Plan (incorporated by reference to Exhibit
  10.5 to the Registrant's Registration Statement on Form
  S-1
  (File
  No.
  333-259973)
  filed with the Securities and Exchange Commission on October
  18, 2021)
  99.2
  2021 Employee Stock Purchase Plan (incorporated by reference to Exhibit
  10.8 to the Registrant's Registration Statement on Form
  S-1
  (File
  No.
  333-259973)
  filed with the Securities and Exchange Commission on October
  18, 2021)
  99.3
  Amended and Restated 2022 Inducement Stock Incentive Plan (incorporated by reference to Exhibit 
  10.9 to the Registrant's Annual Report on Form
  10-K
  (File No. 001-40925) filed
  with the Securities and Exchange Commission on March 11,
  2025)
  107*
  Filing Fee Table
  *
  Filed herewith
  SIGNATURES
  Pursuant to the requirements of the Securities Act of 1933, as amended, the registrant certifies that it has reasonable grounds to believe that it meets all
  of the requirements for filing on
  Form S-8 and
  has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Waltham,
  Commonwealth of Massachusetts on this 11th day of March, 2025.
  XILIO THERAPEUTICS, INC.
  By:
  /s/ René Russo
  René Russo
  President and Chief Executive Officer
  POWER OF ATTORNEY AND SIGNATURES
  We, the undersigned officers and directors of Xilio Therapeutics, Inc., hereby severally constitute and appoint René Russo and Caroline Hensley,
  and each of them singly (with full power to each of them to act alone), our true and lawful attorneys with full power of substitution and resubstitution in each of them for him and in his name, place and stead, and in any and all capacities, to sign
  for us and in our names in the capacities indicated below, the registration statement on
  Form S-8 filed
  herewith and any and all subsequent amendments to said registration statement, and generally to
  do all such things in our names and on our behalf in our capacities as officers and directors to enable Xilio Therapeutics, Inc. to comply with the provisions of the Securities Act of 1933, as amended, and all requirements of the Securities and
  Exchange Commission, hereby ratifying and confirming our signatures as they may be signed by our said attorneys, or any of them, to said registration statement and any and all amendments thereto.
  Pursuant to the requirements of the Securities Act of 1933, as amended, this registration statement has been signed by the following persons in the capacities
  and on the dates indicated.
  Signature
  Title
  Date
  /s/ René Russo
  René Russo
  President and Chief Executive Officer, Director
  (Principal Executive Officer)
  March 11, 2025
  /s/ Christopher Frankenfield
  Christopher Frankenfield
  Chief Financial Officer and Chief Operating Officer
  (Principal Financial Officer)
  March 11, 2025
  /s/ Kevin Brennan
  Kevin Brennan
  Senior Vice President, Finance and Accounting
  (Principal Accounting Officer)
  March 11, 2025
  /s/ Paul J. Clancy
  Paul J. Clancy
  Chair of the Board of Directors
  March 11, 2025
  /s/ Sara M. Bonstein
  Sara M. Bonstein
  Director
  March 11, 2025
  /s/ Aoife Brennan
  Aoife Brennan
  Director
  March 11, 2025
  /s/ Daniel Curran
  Daniel Curran
  Director
  March 11, 2025
  /s/ Robert Ross
  Robert Ross
  Director
  March 11, 2025
  /s/ Christina Rossi
  Christina Rossi
  Director
  March 11, 2025
  /s/ James Shannon
  James Shannon
  Director
  March 11, 2025
  /s/ Yuan Xu
  Yuan Xu
  Director
  March 11, 2025