Advances in the understanding of the pathophysiology of psoriasis have led to the development of biologic therapies that target key components of the immune system involved in the inflammatory cascade of psoriasis, revolutionizing the management of moderate-to-severe cases. Alongside biologics, small molecules have emerged as promising treatment options. However, despite significant progress, several challenges remain. Additionally, long-term safety data for many newer agents are still lacking, necessitating ongoing surveillance and real-world evidence collection. This narrative review, performed by analysing the existing medical literature using PubMed, Ovid, Scopus, Embase and Cochrane Library databases up to 30 June 2025, explores new systemic therapies for psoriasis, including both approved and emerging biologics and small molecules, highlighting future directions in treatment. Despite advancements in psoriasis treatment, unmet needs persist, including specific clinical phenotypes such as pustular psoriasis, paradoxical reactions, patient comorbidities, treatment resistance or inefficacy, and high costs, underscoring the need for novel and emerging therapies. In the future, advances in pharmacogenetics and artificial intelligence could revolutionize psoriasis management. Artificial intelligence-driven models integrating clinical data, laboratory findings and biomarkers could enhance precision medicine by optimizing treatment selection and establishing standardized therapeutic algorithms, ensuring that patients receive the right drug at the right time.
