Nanoprobes for efficient tumor-targeted imaging and therapy are urgently needed for clinical tumor theranostics. Herein, inspired by the heterogeneity of the tumor microenvironment, we report a covalent organic framework (COF)-derived biomimetic nanozyme for precise tumor-targeted imaging and NIR-II photothermal-catalysis-enhanced chemotherapy (PTCEC). Using a crystalline nanoscale COF as the precursor, a peroxidase-like porous N-doped carbonous nanozyme (PNC) was obtained, which was cloaked with an M1 macrophage cell membrane (M1m) to create a multifunctional biomimetic nanoprobe for tumor-targeted imaging and therapy. The M1m coating enabled the nanoprobe to target cancer cells and tumor tissues for highly efficient tumor imaging and drug delivery. The peroxidase-like activity of the PNC allowed for the conversion of intratumoral H2O2 into toxic ˙OH that synergized with its NIR-II photothermal effect to strengthen the chemotherapy. Therefore, highly efficient tumor-targeted imaging and NIR-II PTCEC were realized with an M1 macrophage mimic nanoprobe. This work provides a feasible tactic for a biomimetic theranostic nanoprobe and will inspire the development of new bioactive nanomaterials for clinical tumor theranostic applications.