The　application　of　2D　MXene　materials　in　the　biomedical　field　has　been　widely　explored.　Apart　from　excellent　photothermal　properties,　their　role　in　modulating　various　immune　cells　and　overcoming　immune-suppressive　tumor　microenvironments　is　waiting　to　be　discovered.　In　this　work,　a　novel　multifunctional　2D　vanadium　carbide　is　constructed　that　degrades　in　situ　in　the　tumor　microenvironment.　Various　characterizations　and　first-principles　calculations　indicated　that　V4C3　nanosheets　exhibit　excellent　light　absorption　and　photothermal　conversion　capabilities　in　the　NIR-II　biological　window.　The　photothermal　and　X-ray　absorption　properties　of　V4C3　nanosheets　enabled　dual-modal　photoacoustic　imaging/computerized　tomography　(PA/CT)　imaging　functionality.　The　V4C3　nanosheets　in　the　tumor　microenvironment　decomposed　under　the　effect　of　H2O2　and　GSH,　triggering　a　Fenton-like　reaction.　The　photothermal　ablation　and　reactive　oxygen　species　(ROS)　generation　capabilities　enabled　V4C3　nanosheets　to　convert　cold　tumors　into　hot　ones　(macrophage:　M2→M1)　and　induce　reactions　like　immunogenic　cell　death　(ICD).　Dendritic　cell　(DC)　cells　matured　under　the　ICD　stimulation,　which　promoted　T　cell　activation,　reduced　Treg　cells　and　thus　effectively　enhanced　tumor　immunotherapy.　The　multiple　properties　including　imaging,　photothermal,　enzyme-driven,　and　immune　functions　enable　V4C3　nanosheets　to　ablate　tumors　effectively.　This　study　provides　an　example　for　the　research　of　the　multifunctional　exploration　and　application　of　MXene　in　biomedicine　filed.　©　2024　Wiley-VCH　GmbH.