Background <p>Extracellular vesicles (EVs), such as exosomes, have been extensively discovered for their function in various diseases and potential therapeutic properties. In this review, we aimed to describe the therapeutic roles of functionalized exosomes in cancer and regenerative medicine.</p> Methods <p>In this review study, we studied numerous articles over the past two decades published on the application of exosomes in different diseases, as well as on perspectives and challenges in this field.</p> Results <p>Recent advancements have shown that exosomes can be used as a drug delivery system. However, this approach faces challenges such as low efficiency and non-targeting effects. Different methods, including genetic, chemical, and physical modifications, are used to functionalize exosome surfaces to address these limitations. In some cases, a combination of modification methods has been used to produce smart exosomes. Different therapeutic agents have been inserted on exosome surfaces by different modification methods. These functionalized exosomes can effectively deliver therapeutic agents to target cells. A growing body of evidence shows that functionalized exosomes are promising for cancer therapy and regenerative medicine. They can not only effectively deliver therapeutic agents to cancer cells, inhibiting tumorigenesis, but also efficiently contribute to tissue repair and regeneration by increasing cell proliferation and angiogenesis. In this review, we discuss different modification methods used to functionalize exosomes and related studies. In addition, we describe the application of functionalized exosomes in cancer and regeneration, along with challenges and perspectives.</p> Conclusions <p>Although functionalized exosomes show promising results, further studies are essential for the clinical translation of these exosomes.</p>