Current nanodrug-based cancer therapy is susceptible to the problems of rapid clearance from circulation and limited therapeutic efficacy. Herein, we report a magnetically targeted and photothermal-triggered drug release nanotheranostics system based on superparamagnetic iron oxide (FeO), IR780, doxorubicin (DOX), and perfluoropentane (PFP) entrapped poly-lactide- co-glycolide (PLGA) nanoparticles (IR780/FeO@PLGA/PFP/DOX NPs) for triple-modal imaging-guided synergistic therapy of breast cancer. In this work, IR780 and FeO convert light into heat, which triggers DOX release from IR780/FeO@PLGA/PFP/DOX NPs and a phase-shift thermoelastic expansion of PFP; this procedure further accelerates the DOX release and tissue extrusion deformation. FeO NPs also serve as the target moiety by an external magnet directed to the tumor. Specifically, the IR780/FeO@PLGA/PFP/DOX NPs can be used for triple-modal imaging, including near infrared fluorescence, magnetic resonance, and ultrasound. Furthermore, the antitumor therapy studies reveal the extraordinary performance of IR780/FeO@PLGA/PFP/DOX NPs in magnetically targeted synergistic chemo-photothermal therapy of cancer. Therefore, the multifunctional IR780/FeO@PLGA/PFP/DOX NPs guided by the magnetic field show a great potential for cancer theranostics.