We herein explored a smart Fe-HPPy@Au/DOX theranostic agent for CT diagnosis and PTT/chemotherapy/CDT synergistic treatment of cancer. When the Fe-HPPy@Au/DOX theranostic agent entered the tumor, the tumor environment accelerated the trapped Fe ions release to catalyze the production of ˙OH for CDT. NIR irradiation drove the PTT, and at the same time improved the CDT by increasing the production of ˙OH and triggered DOX release for chemotherapy. In addition, the Au nanoparticles on the surface of Fe-HPPy@Au nanocomposites could be used as a CT imaging agent and catalyzer to produce H2O2 for enhanced CDT.