BACKGROUND: The advancement of biomimetic drug delivery systems designed for biomedical applications has attracted considerable attention from researchers in recent years. A particularly noteworthy approach involves the use of various cell membranes, which can impart distinctive functionalities to the nanoparticles, including specific recognition of target cells, prolonged circulation within the bloodstream, and enhanced ability to evade the immune system, as surface coatings on nanoparticles. This innovative strategy has positioned cell membrane-coated nanoparticles (CMCNPs) as a promising framework for addressing a wide range of diseases more effectively. METHODS: In the current investigation, lipid nanoparticles were specifically engineered using glioblastoma cell membrane (GBMM) coatings, termed as LNPs/D@GBMM, to serve as targeted nanotheranostics against homologous malignant glioblastoma (GBM). The physicochemical properties of LNPs/D@GBMM were investigated in terms of particle size, morphology, drug loading (DL), drug release behavior and so on. Homologous cellular uptake was evaluated by confocal laser scanning microscopy (CLSM). Cell cytotoxicity was evaluated by MTT assay. Moreover, the bio-distribution of CMCNPs in vivo was investigated via the near-infrared (NIR) fluorescence imaging technique, and the anti-tumor effect in vivo was evaluated in xenografted nude mice. RESULTS: Compared to non-targeted lipid nanoparticles, LNPs/D@GBMM exhibited superior cytotoxic effects against homologous tumor cells. In addition, fluorescence imaging of targeted tumor cells treated with LNPs/D@GBMM indicated a marked increase in cell internalization, and improved fluorescence distribution in vivo. LNPs/D@GBMM finally produced an excellent tumor suppression effect on homologous tumors. CONCLUSION: The robust platform established by CMCNPs leveraging the inherent characteristics of homologous tumor cell membranes, is expected to facilitate systemic delivery of therapeutic agents specifically aimed at treating tumors, thus advancing the efficacy of cancer therapy in clinical settings.