Developing efficient integrated diagnosis and treatment agents based on the fuel‐free self‐movement nanomotors remains challenging in antitumor therapy. In this study, we report a covalent organic framework (COF)‐based biomimetic nanomotor composed of PPy core, porphyrin‐COF shell and HCT116 cancer cell membrane coating. Under NIR light irradiation, the obtained mPPy@COF‐Por can overcome Brownian motion and achieves directional motion through self‐thermophoretic force generated from the PPy core. The HCT116 cancer cell membrane coating enables the nanomotor to selectively recognize the source cell lines and reduces the bio‐adhesion of mPPy@COF‐Por in biological medium, endowing with this NIR light‐powered nanomotor a good mobility. More importantly, such multifunctional integration allows the COF‐based nanomotor to be a powerful nanoagent for cancer treatment, and the high IRI/PAI/FLI trimodal imaging guided combined PTT/PDT therapeutic effect on HCT116 tumor cell is successfully achieved. Our results offer considerable promise for the development of COF‐nanomotors with integrated imaging/therapy modalities in biomedical applications.This article is protected by copyright. All rights reserved