Given the insufficient antigenicity and unfavorable nature of the tumor microenvironment (TME), innovative therapeutics are urgently needed to maximize tumoricidal effects. Here, inspired by natural cytochrome c oxidases, we present sonophoto-activable artificial cupreous peroxidases (CuSA-CN) for precise systemic antitumor activation and redox-targeted cancer ablation. Our studies demonstrate that CuSA-CN features highly exposed Cu-N4 sites with semiconducting and porous laminar characteristics to facilitate expedited electron-proton transfer, which generates massive reactive oxygen species in the TME through dual-enzymatic pathways and sonophoto-activation, thus synergistically disrupting the cellular redox landscape and augmenting apoptosis. Accordingly, CuSA-CN with sonophoto-stimulation can effectively induce potent immunogenic cell death, liberating copious tumor-associated antigens, thereby activating systemic antitumor responses, fostering abscopal effects, and establishing durable tumor memory, which ultimately prevents tumor recurrence and metastasis. We validate that this bioinspired design of CuSA-CN possesses a robust and on-demand ability for primary and metastatic tumor ablation, representing a promising therapeutic strategy for precision targeting malignancies.