Photodynamic therapy (PDT) has emerged as a promising cancer treatment modality; however, its therapeutic efficacy is greatly limited by tumor hypoxia. In this study, a metal‐organic framework (MOF)‐based hydrogel (MOF Gel) system that synergistically combines PDT with the supply of oxygen is designed. Porphyrin‐based Zr‐MOF nanoparticles are synthesized as the photosensitizer. MnO2 is decorated onto the surface of the MOF, which can effectively convert H₂O₂ into oxygen. Simultaneously, the incorporation of MnO2‐decorated MOF (MnP NPs) into a chitosan hydrogel (MnP Gel) serves to enhance its stability and retention at the tumor site. The results show that this integrated approach significantly improves tumor inhibition efficiency by relieving tumor hypoxia and enhancing PDT. Overall, the findings underscore the potential for employing nano‐MOF‐based hydrogel systems as promising agents for cancer therapy, thus advancing the application of multifunctional MOFs in cancer treatment.