<p>Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent nodules, abscesses, and sinus tracts that lead to significant morbidity and impaired quality of life. Although both biologic therapies and surgical interventions are effective when used independently, their combined use has gained increasing attention. This systematic review aimed to evaluate the efficacy and safety of combining immunomodulatory therapy with surgical procedures in HS. A conceptual framework was applied that distinguished three modalities of combined treatment according to the temporal relationship between biologic therapy and surgery: pre-biologic surgery, post-induction surgery, and concomitant approaches. A comprehensive search identified eight eligible studies, including 508 patients. Most studies were retrospective and of low methodological quality. Across studies, combination therapy (particularly with adalimumab, secukinumab, or bimekizumab) was generally associated with improved clinical outcomes compared to biologic monotherapy, including higher response rates (Hidradenitis Suppurativa Clinical Response [HiSCR]; 55% reduction in the International Hidradenitis Suppurativa 4 [IHS4-55]), greater reductions in pain, disease flares, and Dermatology Life Quality Index scores. Safety profiles were comparable between groups, with no consistent increase in postoperative complications or serious adverse events. However, key outcomes such as wound healing time were poorly reported. Substantial heterogeneity in study design, treatment protocols, and timing of interventions limited comparability and precluded meta-analysis. Overall, the available evidence preliminarily supports combined medical and surgical treatment as a potentially beneficial and well-tolerated strategy for moderate-to-severe HS, in line with current expert practice. However, given the low quality and substantial heterogeneity of the included studies, these findings should be considered exploratory and require confirmation in higher-quality prospective studies that adopt standardized definitions of combination therapy and report wound healing as a core outcome.</p>