Modulating　the　immunosuppressive　tumor　immune　microenvironment　(TIME)　is　considered　a　promising　strategy　for　cancer　treatment.　However,　effectively　modulating　the　immunosuppressive　TIME　within　hypoxic　zones　remains　a　significant　challenge.　In　this　work,　we　developed　a　hypoxia-responsive　amphiphilic　drug　carrier　using　boron-dipyrromethene　(BODIPY)　dye-modified　chitosan　(CsB),　and　then　fabricated　a　hypoxia-targeted　nanotheranostic　system,　named　CsBPNs,　through　self-assembly　of　CsB　and　pexidartinib　(5-((5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl),　PLX3397),　an　immunotherapeutic　drug　targeting　tumor-associated　macrophages　(TAMs),　for　synergistic　photothermal/immunotherapy　and　hypoxia　imaging.　CsBPNs　demonstrated　uniform　size,　good　stability,　and　hypoxia-switchable　fluorescence　and　photothermal　effects,　enabling　deep　penetration　and　hypoxia　imaging　capacities　in　three-dimensional　tumor　cell　spheres　and　tumor　tissues.　In　vitro　and　in　vivo　experiments　showed　that　CsBPNs　under　laser　irradiation　promoted　TAMs　repolarization,　reversed　the　immunosuppressive　TIME,　and　enhanced　the　therapeutic　outcome　of　PLX3397　in　solid　tumors　by　facilitating　deep　delivery　into　hypoxic　regions　and　synergistic　photothermal　therapy.　This　work　provides　a　new　strategy　for　detecting　and　modulating　the　immunosuppressive　TIME　in　hypoxic　zones,　potentially　enabling　more　precise　and　effective　photo-immunotherapy　in　the　future.　©　2024　Elsevier　Inc.