Novel multifunctional core-shell nanoparticles (NPs) have attracted widespread attention due to their easy-to-modify surface properties and abundant functional groups. This study introduces a facile approach to synthesize Ag@ iron oxide (FeO) @C NPs, and modify with amino-poly (ethylene glycol) (PEG)-carboxyl and folate (FA) on the exposed carbon surface to produce high contrast for excellent stability, good biocompatibility, cancer cell targeting, and synergistic treatment. The multi-armed PEG at the edge of Ag@FeO@C NPs provides the materials an excellent capacity for doxorubicin (DOX) loading. The carbon layer could be used as a photothermal reagent due to its excellent near-infrared (NIR) absorbance capacity, and FeO was used as a reagent for magnetic resonance (MR) imaging. In vivo combination therapy with this agent was administered in a mouse tumor model, and a remarkable synergistic antitumor effect that is superior to that obtained by monotherapy was achieved. Concerning these features together, these unique multifunctional Ag@FeO@C-PEG-FA/DOX NPs could be regarded as an attractive nanoplatforms for chemo-photothermal synergistic tumor therapy with dual-modal fluorescence and MR imaging-guided targeting.