Chemodynamic therapy (CDT) offers a promising alternative to conventional cancer treatment. However, the limited acidity and H2O2 concentration in tumor microenvironment (TME) severely impair the anticancer effects of CDT. In this study, we report a microemulsion-assisted coassembly method to prepare iron(III) tetraphenylporphyrin (FeTPP) and magnetic (Fe3O4) nanocomposite material (FeTPP@Fe3O4), using photoactive FeTPP and Fe3O4 nanocrystals as building blocks. The self-assembling nature of FeTPP results in disordered aggregation and fluorescence quenching, leading to a high light-to-heat conversion efficiency. Continuously, the photo-thermal effect enhances the catalytic decomposition of hydrogen peroxide (H2O2) in the Fenton reaction on Fe3O4 nanocrystals to generate highly toxic hydroxyl radicals (·OH) to destroy cancer cells. This cascade reaction produces a synergistic therapeutic effect between CDT and photothermal therapy (PTT), which significantly amplifies the therapeutic effect and enhances the treatment outcome of cancer patients. The highly efficient tumor catalytic therapy in vivo results confirmed that this nanomedicine treatment is an excellent biocompatible catalytic nanomedicine therapy achieved through a photo-enhanced Fenton reaction activity approach.