The synergistic therapy of chemotherapy and photothermal therapy (PTT) has been reported as a promising antitumor strategy. To achieve effective combination therapy, developing more suitable candidate nanomaterials with optimal photothermal property and high chemical drug loading capacity is very necessary. Herein, a bimetallic PtPd nanoparticle was synthesized with the merits of excellent photothermal effect and mesoporous structure for doxorubicin (DOX) loading. We further designed PtPd-ethylene glycol (PEG)-folic acid (FA)-doxorubicin (DOX) nanoparticle for chemo-photothermal therapy of MCF-7 tumor with folic acid engineering to achieve active targeting. Moreover, excellent photoacoustic (PA) imaging of PtPd-PEG-FA-DOX nanoparticles facilitated the precise in vivo tracking and further evaluation of nanoparticles’ targeting effect. The in vitro and in vivo results both demonstrated PtPd-PEG-FA-DOX nanoparticles serve as a safe and promising system for effective treatment of MCF-7 tumor.