Human　heavy-chain　ferritin　(HFn)　possesses　a　stable　and　uniform　cage-like　structure,　tumor-targeting　properties,　self-assembly　capabilities,　and　biocompatibility,　rendering　it　an　ideal　candidate　for　drug　delivery.　Here,　we　developed　a　dual　modified　HFn-based　nanocage　(DFn)　that　targets　the　urokinase-type　plasminogen　activator　receptor　(uPAR)　and,　at　the　same　time,　is　responsive　to　the　tumor　microenvironment　for　controlled　extracellular　drug　release.　This　DFn　was　used　to　co-encapsulate　a　photosensitizer　(CPZ)　and　a　hypoxia-activated　prodrug　(TPZ),　creating　the　multifunctional　nanoparticles　C/T@DFn.　In　vitro　cellular　assays　demonstrated　that　C/T@DFn　significantly　outperformed　both　unmodified　HFn-based　nanoparticles　and　its　counterpart　without　the　uPARtargeting　motif　in　inhibiting　tumor　cell　survival,　proliferation,　and　migration,　and　showed　enhanced　tumor　cell　spheroids　penetration.　In　vivo　studies　further　demonstrated　the　improved　tumor-specific　accumulation　and　antitumor　efficacy　of　the　loaded　cargo　in　the　DFn　nanocages　in　comparison　with　wild-type　HFn.　This　improved　therapeutic　effect　is　achieved　through　receptor-mediated　targeting　and　tumor　microenvironment-responsive　release　of　the　cargo　from　the　DFn　nanocages,　resulting　in　synergistic　action　of　CPZ　and　TPZ　within　the　tumor　tissue.　Overall,　this　study　introduces　an　ideal　ferritin-based　nanoplatform　for　the　efficient　co-delivery　of　therapeutic　agents,　offering　a　promising　strategy　for　targeted　tumor　therapy.