The main challenges of nanozyme-based tumor catalytic therapy (NCT) lie in the unsatisfactory catalytic activity accompanied by a complex tumor microenvironment (TME). A few nanozymes have been designed to possess both enzyme-like catalytic activities and photothermal properties; however, the previously reported nanozymes mainly utilize the inefficient and unsafe NIR-I laser, which has a low maximum permissible exposure limit and a limited penetration depth. Herein, we report for the first time an all-in-one strategy to realize mild NIR-II photothermally amplified NCT by synthesizing amorphous CoSnO3 nanocubes with efficient triple enzyme-like catalytic activities and photothermal conversion properties. The presence of Co2+ and Sn4+ endows CoSnO3 nanocubes with the triple enzyme-like catalytic activities, not only achieving enhanced reactive oxygen species (ROS) generation through the Co2+-mediated peroxidase-like catalytic reaction to generate ˙OH and Sn4+-mediated depletion of overexpressed GSH, but also realizing the catalytic decomposition of endogenous H2O2 for relieving tumor hypoxia. More importantly, the obtained CoSnO3 nanocubes with a high photothermal conversion efficiency of 82.1% at 1064 nm could achieve mild hyperthermia (43 °C), which further improves the triple enzyme-like catalytic activities of the CoSnO3 nanozyme. The synergetic therapeutic efficacy of the NIR-II-responsive CoSnO3 nanozyme through mild NIR-II PTT-enhanced NCT could realize all-in-one multimodal tumor therapy to completely eliminate tumors without recurrence. This study will open a new avenue to explore NIR-II-photoresponsive nanozymes for efficient tumor therapy.