Photothermal therapy (PTT) has been widely employed in tumor treatment due to the non-invasive, highly selective, and low toxic side effects. However, the limited penetration of laser couples with the metastasis and recurrence of tumors, thus failing to eliminate them. Here, we report that ceria-loaded gold@platinum (CeO/Au@Pt) nanospheres modified with polyethylene glycol (PEG). exhibit dual enzymatic activities for photothermal-catalytic synergistic therapy of tumors. CeO/Au@Pt nanospheres are constructed through the loading of ultra-small CeO into core-shell Au@Pt nanospheres. In such a construct, Au@Pt enables targeted PTT, thanks to exceptional photothermal properties, while CeO nanozymes alleviate tumor hypoxia and kill tumor cells by producing highly toxic hydroxyl radicals (·OH) based on catalase- and peroxidase-like activities. Synergistic photothermal-catalytic therapy is achieved by delivering nanozymes to the tumor microenvironment (TME) coupled with PTT. This photothermal-catalytic approach that combines simultaneous exogenous and endogenous activation is a potential option for tumor co-therapy.