Dermatological drug delivery remains a major challenge due to the complex structure and barrier properties of the skin, particularly the stratum corneum, which limits the penetration of therapeutic agents. In recent years, niosomes, non-ionic surfactant-based vesicular systems, have emerged as a promising approach to overcome these limitations. Niosomes possess a unique bilayer structure that allows encapsulation of both hydrophilic and lipophilic drugs, enabling enhanced stability, controlled release, and targeted drug delivery to specific skin layers. Their biocompatibility, cost-effectiveness, and ability to improve drug retention make them superior to conventional systems such as creams, gels, and liposomes. Recent advancements in niosomal technology, including elastic niosomes, proniosomes, and surface-modified formulations, have further improved their performance in dermatological applications such as acne, psoriasis, fungal infections, and inflammatory conditions. Moreover, the integration of nanotechnology and development of hybrid niosome–hydrogel systems have expanded their potential for both therapeutic and cosmetic use. This review highlights the structural characteristics, formulation strategies, mechanisms of skin targeting, and current research trends in niosome-based drug delivery systems, emphasizing their potential to revolutionize topical and transdermal therapies.