Exosomes are nanovesicles derived from cells that can carry therapeutic agents such as small molecules and nucleic acids for targeted delivery to specific cells or tissues. This review discusses the engineering of exosomes for targeted drug delivery using genetic and chemical methods. Exosomes offer advantages such as low toxicity, low immunogenicity, and high engineerability, making them promising for cell-free therapies. The review covers the biogenesis, secretion, and cellular entry of exosomes, their cargo packaging, surface engineering, and applications in various disease models. Exosomes can be modified through genetic engineering or chemical methods to enhance their targeting capabilities. Genetic engineering involves fusing targeting ligands with exosomal membrane proteins, while chemical modification allows the attachment of various ligands to the exosome surface. Exosomes can be used for targeted delivery of drugs, siRNA, and other therapeutic agents. The review also discusses the potential of exosomes in cancer therapy, including their ability to cross the blood-brain barrier and deliver drugs to specific tumor cells. Exosomes can be modified with targeting peptides, antibodies, or other molecules to enhance their specificity and therapeutic efficacy. The review highlights the challenges and opportunities in exosome-based drug delivery, including the need to understand the impact of surface engineering on exosome stability, cellular entry, and tissue distribution. Exosomes have potential applications in imaging, diagnosis, and combination therapies with anticancer drugs and diagnostic probes. The review concludes that exosome engineering holds great promise for targeted drug delivery and cell-free therapies.Exosomes are nanovesicles derived from cells that can carry therapeutic agents such as small molecules and nucleic acids for targeted delivery to specific cells or tissues. This review discusses the engineering of exosomes for targeted drug delivery using genetic and chemical methods. Exosomes offer advantages such as low toxicity, low immunogenicity, and high engineerability, making them promising for cell-free therapies. The review covers the biogenesis, secretion, and cellular entry of exosomes, their cargo packaging, surface engineering, and applications in various disease models. Exosomes can be modified through genetic engineering or chemical methods to enhance their targeting capabilities. Genetic engineering involves fusing targeting ligands with exosomal membrane proteins, while chemical modification allows the attachment of various ligands to the exosome surface. Exosomes can be used for targeted delivery of drugs, siRNA, and other therapeutic agents. The review also discusses the potential of exosomes in cancer therapy, including their ability to cross the blood-brain barrier and deliver drugs to specific tumor cells. Exosomes can be modified with targeting peptides, antibodies, or other molecules to enhance their specificity and therapeutic efficacy. The review highlights the challenges and opportunities in exosome-based drug delivery, including the need to understand the impact of surface engineering on exosome stability, cellular entry, and tissue distribution. Exosomes have potential applications in imaging, diagnosis, and combination therapies with anticancer drugs and diagnostic probes. The review concludes that exosome engineering holds great promise for targeted drug delivery and cell-free therapies.