Transdermal drug delivery systems offer a noninvasive alternative to oral and parenteral administration routes, providing controlled release and enhanced bioavailability. This chapter investigates the anatomical structure and barrier properties of the skin, elucidates drug permeation mechanisms, and explores formulation strategies for optimizing transdermal delivery. Various technologies are analyzed, including passive systems (patches, gels), active systems (iontophoresis, microneedles), and nanocarrier-based approaches. The chapter delineates evaluation methods, regulatory considerations, and quality control standards. Applications across diverse therapeutic areas, such as cardiovascular diseases, pain management, and hormone therapy, are explored. Key challenges, including overcoming the skin barrier and expanding the range of deliverable drugs, are addressed. Future perspectives highlight the development of intelligent, responsive systems and integration with complementary technologies. In conclusion, transdermal drug delivery demonstrates significant potential for enhancing patient outcomes and revolutionizing drug administration methodologies.