Inflammatory skin diseases (ISDs), such as psoriasis and atopic dermatitis, represent a significant global health burden characterized by complex pathophysiology and a profound impact on patients' quality of life. The cornerstone of treatment often involves topical drug delivery; however, the formidable barrier function of the stratum corneum and the inherent limitations of conventional formulations (e.g., low bioavailability, systemic side effects, poor patient compliance) necessitate advanced delivery strategies. Nano-engineered drug delivery systems (nDDS) have emerged as a transformative approach to overcome these challenges. This review comprehensively examines the latest advancements in nDDS for the topical management of ISDs. We focus on the design, functionality, and mechanistic actions of various nanocarriers, including liposomes, ethosomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and polymeric nanoparticles. The discussion highlights how these systems enhance drug solubility, improve skin penetration and retention, provide controlled release, and reduce off-target effects. Furthermore, we integrate insights from skin pharmacology and toxicology, reviewing the pharmacokinetic/pharmacodynamic (PK/PD) profiles and safety evaluations of these nano-formulations. The translation of nDDS from bench to bedside is explored through the lens of clinical dermatopharmacy, covering aspects from early-phase trial design to pharmacoeconomics and the growing importance of real-world evidence. By synthesizing cutting-edge research with clinical practicality, this review aims to provide a roadmap for the development and application of effective, safe, and patient-centric nano-topical therapies for inflammatory skin conditions.