<p>In the current study, nanoenzymes with multi-enzyme-like activities have garnered significant attention in anti-tumor treatment by responding to the tumor microenvironment. This study reports a kind of high-drug-loading nanoparticles with multiple nanozyme activities. These nanoparticles can respond to the tumor microenvironment and are used for the combined chemotherapy–photothermal–chemodynamic therapy of tumors. In the tumor microenvironment, Fe³⁺/Mn²⁺ bimetallic species can reduce the level of glutathione and simultaneously convert endogenous hydrogen peroxide into hydroxyl radicals through the Fenton reaction, enhancing the efficiency of dynamic therapy. Meanwhile, MnO₂ can decompose hydrogen peroxide under acidic conditions to produce oxygen, alleviating tumor hypoxia. In order to take advantage of the hollow structure of nanoparticles, the chemotherapy drug paclitaxel was loaded into the hollow structure. In vitro studies have shown that nanoparticles have a higher drug release rate under simulated tumor conditions, with the maximum drug release rate reaching 79%, demonstrating the stimuli-responsive decomposition of the nanoparticles. The photothermal conversion efficiency can reach 41.3%, and they also have good CAT and POD activities. Studies at the cellular level have shown that nanoparticles have good cytocompatibility with 4T1 cells and were effectively internalized by breast cancer cells, causing 80% of the cells to die through chemodynamic therapy and photothermal therapy effects. The nanoparticles constructed in this study have broad application prospects in building drug-loaded composite nanomaterials with multiple functions for the treatment of tumors.</p>