<p>Chronic urticaria (CU) is a complex, disabling skin disease characterized by recurrent, pruritic wheals and frequently angioedema lasting for 6 weeks or more. Although non‐sedating H1‐antihistamines remain the first‐line therapy, a significant subset of patients (50%) remains symptomatic despite antihistamines, underscoring an unmet need for more targeted treatments. Recent advances in our understanding of CU pathophysiology have led to the development of biologic agents—most notably omalizumab and dupilumab—as well as an expanding pipeline of small‐molecule therapies targeting key intracellular signaling pathways (e.g., Bruton’s tyrosine kinase [BTK] and Janus kinase [JAK] inhibitors). Therapeutic targets for biologics in chronic spontaneous urticaria (CSU) include IgE, IL-4/IL-13, and IL-5 pathways. This review provides a comprehensive overview of the underlying immunopathogenesis of CSU in adults, critically examines the limitations of conventional therapy (primarily second-generation H1-antihistamines), and reviews the current status and future prospects of biologic and small‐molecule treatments. It synthesizes the rapidly evolving landscape of these therapies focusing on therapeutic mechanisms of biologic and small-molecule therapies, recent clinical trial data, and potential for personalized treatment, building on and extending prior reviews. We also discuss practical considerations—including endotyping, cost‐effectiveness, and long‐term safety, and outline future research directions toward personalized management of chronic urticaria.</p>