<p>Skin cancer is one of the most prevalent malignancies worldwide, posing significant challenges to effective treatment due to limited drug penetration, systemic toxicity, and patient non-compliance. Transferosomes, a class of ultra-deformable vesicular carriers, have emerged as a promising strategy to overcome the skin barrier and improve topical and transdermal drug delivery. This review discusses the structural composition, preparation techniques, and physicochemical properties of transferosomes, emphasizing their unique mechanism of skin penetration. We summarize current research on transferosome-based formulations for delivering chemotherapeutics, photosensitizers, and natural bioactives targeting various skin cancers, including melanoma, basal cell carcinoma, and squamous cell carcinoma. Comparative analyses highlight the advantages of transferosomes over conventional vesicular systems such as liposomes and niosomes, including improved skin permeability, enhanced drug retention, and reduced systemic toxicity. Preclinical and limited clinical studies demonstrate their potential in achieving localized and sustained anticancer effects. Challenges related to formulation stability, large-scale production, and clinical translation are discussed, along with emerging approaches such as ligand functionalization and microneedle-assisted delivery. Collectively, transferosomes represent a versatile and effective nanocarrier system that holds great promise for improving the therapeutic outcomes of skin cancer treatment.</p>