Multidisciplinary investigations have confirmed the critical role of skin barrier dysfunction in the pathogenesis of various chronic dermatoses. However, the heterogeneity in disease presentation, inconsistent assessment criteria, and the lack of therapeutic standardization across clinical settings limit the universal applicability of current findings. The aim of this review is to evaluate the pathophysiological basis of skin barrier impairment in chronic skin conditions, assess the clinical efficacy of emerging therapeutic strategies, and address ongoing challenges and future directions. Skin barrier dysfunction underlies the initiation and perpetuation of inflammatory dermatoses such as atopic dermatitis, psoriasis, and ichthyoses, where disruptions in lipid composition, filaggrin deficiency, and impaired tight junction integrity contribute to disease chronicity. Innovative treatment approaches, including targeted biologics, barrier-repair emollients, and microbiome-modulating therapies, have demonstrated encouraging results in restoring barrier function and controlling inflammation. Emerging nanotechnological and gene-editing therapies offer promising frontiers for precision skin repair. Evidence supports that restoration of the barrier not only alleviates clinical symptoms but also reduces flare frequency and improves patient quality of life. Despite progress, therapeutic implementation faces obstacles such as patient adherence variability, lack of long-term outcome data, and inter-study inconsistencies in outcome measures. This review emphasizes the necessity of standardized protocols and unified barrier assessment tools to enhance clinical translation. The growing body of evidence advocates for integrating barrier-targeted strategies as a central element in the management of chronic dermatoses, thereby improving disease control and overall dermatological care.