INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a substantial impact on patients' quality of life (QoL). This study aimed to characterize the burden of moderate-to-severe AD in the Portuguese population, focusing on patients' QoL and socioeconomic activities while describing their treatment patterns and healthcare resource use. METHODS: This multicenter, cross-sectional, and non-interventional study in eight Portuguese referral AD centers recruited patients over 12 years old, seeking first-time AD care. Patients over 16 years old were analyzed, and data on demographics, clinical characteristics, treatment patterns, healthcare resource utilization, and burden of disease via patient-reported outcomes (PROs) were collected. RESULTS: With a predominantly White cohort, a mean age of 30.0 years, and balanced gender distribution, the study highlighted the significant impact of moderate-to-severe AD on patients' QoL, with a mean Dermatology Life Quality Index score of 15.19. High levels of itch, lesional skin severity, sleep disturbance, and pain contributed to the substantial burden of disease. Productivity was impaired in 40.0% of patients and daily activities were disrupted in 50.0%. Average body surface area involvement was 45.82%, with a mean of 6.49 AD flares in the previous year. Dermatologists played a pivotal role in the patient journey, contributing significantly to the diagnosis (55.9%) and referral process (70.9%). Treatment patterns highlighted a historical reliance on topical therapies and an evolving landscape with post-visit inclusion of advanced therapies such as dupilumab (38.5%), conventional immunosuppressants like cyclosporine (31.2%), and baricitinib (6.8%). CONCLUSION: This study unveils the intricate landscape of moderate-to-severe AD in Portugal, highlighting a substantial unmet need for optimal disease management. The role of dermatologists is crucial, yet limited adoption of advanced therapies in the face of significant disease burden prompts critical reflection.