<p>Skin cancer continues to be among the top malignancies diagnosed around the world, with rising incidence through the years. The cause of most deaths is the metastatic progression, which commonly limits the success of the treatments available. The commonly used methods of surgery, radiotherapy, and immunotherapy, photodynamic and conventional chemotherapy have improved the patient survival rates tremendously. However, the systemic toxicities and therapeutic resistance limit therapeutic efficacy of these treatments. Hence, developing targeted solutions is essential that tackle these concerns directly. Targeted exosomes as extracellular vesicles (EVs) are unique biological nanocarriers for the direct cell delivery of chemo, nucleic acids, and immune modifiers to tumor cells. The purpose of this review is to survey the literature and examine current exosome research in cancer has to offer, especially in relation to improving focused drug delivery, immune modification, tumor microenvironment (TME) alteration, and skin cancer immunotherapy. We describe evidence from preclinical and developing clinical studies showing the exosome-mediated delivery systems improve the bioavailability of a drug. This occurs through its specificity for tumors, mitigate the systemic toxicity of the drug, and neutralize the mechanisms of immune- and chemotherapy resistance. These new approaches to therapy represent a significant advancement in dermatologic oncology and are likely to improve prognosis and patients’ quality of life.</p>