The tumor hypoxic microenvironment (THME) has a profound impact on tumor progression, and modulation of the THME has become an essential strategy to promote photodynamic therapy (PDT). Here, an oxygen self-supplied nanodelivery system that is based on nanometal-organic frameworks (nMOFs) with embedded AuNPs (Au@ZIF-8) on the nMOF surface as a catalase (CAT)-like nanozyme and encapsulating Ce6 inside as a photosensitizer was found to mitigate tumor hypoxia and reinforce PDT. As soon as Au@ZIF-8 reaches the tumor site, the AuNP nanozyme can catalyze excessive H2O2 to produce O2 to alleviate tumor hypoxia, promoting the production of 1O2 with strong toxicity toward tumor cells under irradiation. Our study demonstrates that nMOFs embellished with a nanozyme have great potential for overcoming the THME for cancer therapeutics, which provides a facile strategy for accurate bioimaging and cancer therapy in vivo.