Introduction: Chronic urticaria (CU) is a debilitating skin disorder characterized by recurrent wheals, redness, and intense itching that persist for more than six weeks. While the role of the immune system in CU has been extensively studied, emerging evidence suggests that the skin microbiome may also play a critical role in the development and progression of CU. This study aims to explore the role of the skin microbiome in the pathophysiology and treatment response of CU.Objective: To investigate the relationship between skin microbiome composition and CU pathophysiology, as well as to assess how the microbiome affects the treatment response in a cohort of 65 patients with chronic urticaria.Methodology: A cross-sectional study was conducted and skin swabs were collected from 65 CU patients, and the microbiome composition was analyzed using 16S rRNA gene sequencing. Data on patient demographics, disease severity, and treatment response were also collected.Results: The analysis revealed significant differences in the composition of the skin microbiome between CU patients and healthy controls. Patients with CU showed reduced diversity and an increased abundance of Staphylococcus aureus, which was associated with greater disease severity. Treatment responders had higher microbial diversity compared to non-responders.Conclusion: The findings highlight the potential role of the skin microbiome as a biomarker for CU pathophysiology and treatment response. Therapeutic strategies that target the microbiome may offer new avenues for improving disease management.