Photodynamic therapy (PDT) with photosensitizers has been considered an effective strategy for treating tumors by generating reactive oxygen species (ROS) to induce tumor cells apoptosis or necrosis. However, the poor water solubility, rapid blood clearance, and lack of effective targeting of the photosensitizer are still a serious challenge for its satisfactory anti-cancer efficacy. Herein, we fabricated a stem cell membrane–camouflaged gelatin nanogels (Ng), which integrating the drug loading capacity of Ng and targeting ability of stem cell membrane, endowed with many unique advantages for targeted drug delivery. This bioinspired drug delivery system composed of hydrophobic photosensitizer, chlorin e6 (Ce6)-loaded gelatin nanogels (Ng) (Ng/Ce6), as the inner cores and coated stem cell membrane vesicles (SCV) as the outer shells, noted as Ng/Ce6@SCV. The averaged hydrodynamic diameter of Ng/Ce6@SCV was 202.7 ± 11.7 nm (polydispersity index (PDI) = 0.113). Ng/Ce6@SCV could efficiently promote the cellular internalization of Ce6, and generate enough ROS in the tumor cells after near infrared (NIR) laser irradiation, which could efficiently suppress the growth of A549 tumor cells in vitro. After administration, Ng/Ce6@SCV exhibited targeting accumulation and long-term retention at tumor tissues, which was related to the immune escape and tumor targeting ability of the stem cell membrane. The in vivo anti-tumor activity results also demonstrated the enhanced anti-tumor effect of Ng/Ce6@SCV after NIR irradiation by significantly suppressed the primary tumor growth with minimal side effects. All the results indicated this polyphosphoester-based bioinspired nanodrug delivery system could be a suitable strategy for precise and effective PDT of cancers.