Cell membrane-derived nanovesicles (CMNVs) represent a broad category of membrane-bound nano-sized particles. They encompass exosomes, ectosomes, and CMNV-mimetic nanoparticles. The lumen and surface of nanovesicles are enriched with bioactive biomolecules, including proteins, lipids, enzymes, metabolites, nucleic acids, and cell-specific receptors, depending on the source cell. Natural and mimetic CMNVs hold substantial promise in biomedical applications owing to their unique biochemical composition, bio-interfacing properties, circulation stability, and strong protection of cargo. Despite their promise, the clinical use of natural and mimetic CMNVs is challenged by heterogeneous cargo, limited tissue targeting, and the inability to harness all advantages from a single parent cell due to variations in surface markers and biochemical composition. These limitations reduce therapeutic efficacy, emphasizing the need for advanced surface modification and cargo engineering strategies to enhance the biomedical features of CMNVs. This chapter outlines methods for the purification of natural CMNVs and explores various pre-modification (genetic engineering, metabolic glycoengineering, pre-cargo engineering) and post-modification strategies (covalent conjugation, lipid insertion, membrane fusion, post-cargo engineering) to optimize the surface properties and drug-loading capabilities of engineered nanovesicles. Furthermore, this chapter discusses therapeutic potential of engineered CMNVs in addressing cancer, neurological disorders, inflammatory diseases, and promoting tissue regeneration.