The construction of high-efficiency tumor theranostic platform will be of great interest in the treatment of cancer patients; however, significant challenges are associated with developing such a platform. In this study, we developed high-efficiency nanotheranostic agent based on ferroferric oxide, manganese dioxide, hyaluronic acid and doxorubicin (FMDH-D NPs) for dual targeting and imaging guided synergetic photothermal-enhanced chemodynamic/chemotherapy for cancer, which improved the specific uptake of drugs at tumor site by the dual action of CD44 ligand hyaluronic acid and magnetic nanoparticles guided by magnetic force. Under the acidic microenvironment of cancer cells, FMDH-D could be decomposed into Mn2+ and Fe2+ to generate •OH radicals by triggering a Fenton-like reaction and responsively releasing doxorubicin to kill cancer cells. Meanwhile, alleviating tumor hypoxia improved the efficacy of chemotherapy in tumors. The photothermal properties of FMDH generated high temperatures, which further accelerated the generation of reactive oxygen species, and enhanced effects of chemodynamic therapy. Furthermore, FMDH-D NPs proved to be excellent T1/T₂-weighted magnetic resonance imaging contrast agents for monitoring the tumor location. These results confirmed the considerable potential of FMDH-D NPs in a highly efficient synergistic therapy platform for cancer treatment.