The skin, the human body's largest organ, provides an exceptional interface for drug delivery, offering a non-invasive route for both local and systemic therapies. However, the formidable barrier function of the stratum corneum (SC) severely restricts the bioavailability of conventional topical formulations. Overcoming this barrier is the paramount challenge in dermatopharmacology. This review comprehensively explores the cutting-edge advancements in drug delivery systems engineered for cutaneous application. We focus on three pivotal technological domains: (1) enhanced topical formulations leveraging nanocarriers like liposomes, niosomes, and lipid nanoparticles; (2) transdermal drug delivery systems (TDDS) designed for controlled systemic administration; and (3) the revolutionary microneedle (MN) technology, which creates transient micro-conduits for painless and efficient intradermal drug deposition. We delve into the mechanisms of action, recent formulations, and clinical translations of these systems. Furthermore, we discuss the integration of smart stimuli-responsive strategies and the application of these technologies in managing diverse skin disorders, including psoriasis, atopic dermatitis, skin cancer, and alopecia, as well as in cosmeceuticals and vaccines. The convergence of biomaterials science, pharmaceutics, and precision medicine is paving the way for a new era of targeted, effective, and patient-compliant dermatological therapies.