Psoriasis and atopic dermatitis (AD) are chronic immune-mediated inflammatory skin diseases that can substantially impair quality of life. Over the past two decades, their systemic treatment has undergone major changes, driven by advances in the understanding of their pathophysiology and the identification of specific therapeutic targets.

To provide a narrative overview of the systemic treatments currently available or under development for psoriasis and AD in adults and children, describing their mechanisms of action, therapeutic positioning, efficacy, and main safety considerations.

Systemic treatment has progressively evolved from broad immunosuppressive and immunomodulatory agents, such as methotrexate and ciclosporin, toward increasingly selective targeted therapies. In psoriasis, this evolution has led to biologics targeting TNF-α, IL-12/23, IL-17, IL-23 and IL-36, as well as oral targeted therapies including PDE4 and TYK2 inhibitors. In AD, therapies targeting IL-4/IL-13, IL-13 and IL-31 have expanded treatment options, while oral JAK inhibitors provide rapid and effective control of both skin inflammation and pruritus. These advances have progressively extended to pediatric populations, although conventional systemic treatments remain frequently used in children. The growing number of available therapies has also increased the need for comparative evidence. Network meta-analyses suggest particularly high efficacy of IL-17 and IL-23 inhibitors in psoriasis, while JAK inhibitors and IL-4/IL-13-targeted therapies are among the most effective options for AD. However, indirect comparisons should be interpreted cautiously because of heterogeneity between trials, limited long-term safety data, and the paucity of head-to-head studies.

The systemic treatment landscape of psoriasis and AD has shifted from non-specific immunosuppression toward targeted and increasingly personalized approaches. Future research should address long-term treatment strategies, rare adverse events, patient-reported outcomes, and clinical and biological factors that may guide individualized treatment selection.