Biomimetic nanotechnology through camouflaging synthetic nanoparticles (NPs) with natural cell membranes, which bestows with immune evasion and superior targeting capacity, has been extensively used in drug delivery systems (DDS) over the last decades. These biomimetic NPs not only retain the physicochemical features of the synthetic vehicles but also inherit the cell membranes' intrinsic functionalities. Combined with these benefits, optimized nano-biomimetic DDS allow maximum delivery efficacy. Compared to erythrocyte/cancer single cell membrane, the hybrid cell membrane expressing CD47 membrane protein and self-recognition molecules, from erythrocytes and cancer cells, provides remarkable features to the synthetic vehicles, such as immune evasion, long-term circulation, and homotypic targeting. In this review, we describe the preparation strategies, the camouflaging mechanism, and the antitumor applications of hybrid cell membrane-camouflaged NPs. Moreover, we discuss further modification of the hybrid cell membrane and the surface properties of fusion cellular membranes. Finally, we summarize the primary challenges and opportunities associated with these NPs. STATEMENT OF SIGNIFICANCE: Camouflaging synthetic nanoparticles with hybrid cell membrane has been extensively highlighted in recent years. The resultant biomimetic nanoparticles not only reserve the physicochemical properties of the synthetic nanoparticles but also inherit the biological functions of source cells. Compared with single cell membrane, hybrid cell membrane can endow synthetic nanoparticles with multiple biofunctions derived from the original source cells. To provide a timely review of this rapidly developing subject of research, this paper summarized recent progress on the hybrid cell membrane-camouflaged nanoparticles as drug delivery systems for cancer diagnosis and treatment. In this review, we focused primarily on five different types of hybrid cell membrane-camouflaged nanoparticles with the preparation strategies, the camouflaging mechanism, and the antitumor applications. Moreover, further modification of the hybrid cell membrane was also discussed for isolating effectively circulating tumor cells.