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[Display omitted] • Ce and S-doped Bi 2 O 3 nanosheets (BOSC) with oxygen defects are designed and synthesized. • Oxygen vacancies enhance the charge transfer and light absorption capacity. • Cascade conversion of reactive oxygen species is realized via band bending. • BOSC exhibits a variety of enzyme-like activities, leading to tumor oxidative stress amplification. • BOSC can initiate inflammatory programmed cell death, known as PANoptosis. Photocatalytic therapy (PCT) is a minimally invasive technique that utilizes reactive oxygen species (ROS) to selectively and optically impair tumor cells. However, the limited efficacy of photocatalysts hinders their more comprehensive application. In this study, we successfully synthesized Ce and S-doped Bi 2 O 3 (BOSC) nanosheets through topological synthesis. BOSC exhibits CAT-like and POD-like enzyme activities and can generate ROS and heat upon near-infrared light irradiation, thereby amplifying tumor oxidative stress. Introducing rare earth Ce element enhances light absorption, introduces oxygen vacancies, reduces bandgap, and facilitates charge separation. This Ce-doping also modifies the band position and Fermi level of BOSC, resulting in increased band bending at the solid–liquid interface, enabling a cascade reaction of ROS and enhancing ROS production. Additionally, BOSC demonstrates multiple enzyme activities by depleting GSH and catalyzing the production of ROS and O 2 from endogenous H 2 O 2 , thereby exacerbating cellular oxidative damage. The synergistic effect of BOSC post-illumination induces panoptosis, thereby improving the therapeutic efficacy against tumors. This strategy, involving the modulation of band structure and band bending through ion doping to introduce oxygen defects into the photosensitizer, provides a viable approach to enhance tumor phototherapy. [ABSTRACT FROM AUTHOR]