Traditional anticancer treatments fail to significantly improve prognoses, and exploration of novel promising therapeutic modalities is urgently needed. In this study, multifunctional mesoporous polydopamine nanoparticles (Pt@MPDA/GOx/Fe³⁺ NPs) loaded with glucose oxidase (GOx), Fe ions and ultrasmall Pt nanoparticles (NPs) were prepared for magnetic resonance imaging (MRI)-guided photothermal therapy (PTT)-enhanced chemodynamic therapy (CDT). The oxidation of intratumoral glucose to H₂O₂ and GOx induced an H₂O₂-rich microenvironment, and then elevated H₂O₂ was catalyzed into highly cytotoxic ·OH by Fe³⁺ via a Fenton reaction for CDT to induce cancer cell death efficiently. Notably, the heat generated by MPDA NPs under laser irradiation offered a moderate PTT to cascade the CDT effect. Moreover, Pt NPs can oxidize H₂O₂ to yield O₂, which in turn accelerates the catalytic process of GOx to increase the efficiency of CDT. Meanwhile, in the high oxidation environment of tumor cells, Pt NPs are oxidized into Pt²⁺ to achieve a tumor chemotherapy effect. In addition, chelated Fe³⁺ endows the system with an MRI-visible function to monitor the treatment efficacy. In conclusion, this study provides a novel MRI-guided PTT-enhanced CDT synergistic nanomedicine platform for cancer therapy.