BACKGROUND: In recent years, transdermal drug delivery systems (TDDS) have gained popularity as a non-invasive, patient-friendly medication delivery method. OBJECTIVE: This review article examines the latest transdermal medication delivery developments and breakthroughs. The review begins with a brief summary of transdermal medication administration, stressing the skin's barrier role and drug permeation methods. Novel materials and methods improve drug solubility, stability, and skin permeability in formulation technologies. METHODS: A literature review of the most recent innovations in TDDS, such as nano-based delivery systems, microneedles, and smart patches, was conducted. Major challenges of drug solubility, stability, and skin permeability were carefully discussed, along with the transdermal patch designs of new therapeutic applications in pain management, cardiovascular diseases, and hormone therapy. RESULTS: Transdermal medication delivery difficulties may be overcome via nano-based drug delivery systems, microneedle arrays, and smart patches. Furthermore, the paper discusses current advances in transdermal patch design for therapeutic applications, highlighting effective instances in pain management, cardiovascular illness, and hormone therapy. CONCLUSION: The article examines transdermal medication delivery regulations, safety, and patient compliance in addition to technological advances. The complete study in this review seeks to help academics, doctors, and pharmaceutical professionals understand transdermal drug delivery and its future. Understanding recent advances in this field can help stakeholders design more effective and patient-friendly transdermal drug delivery systems, enhancing treatment outcomes and patient well-being.