Introduction <p>Dissecting cellulitis of the scalp (DCS) is a chronic, relapsing neutrophilic scarring alopecia within the follicular occlusion spectrum. It shares clinical and pathogenic features with hidradenitis suppurativa (HS), acne conglobata, and pilonidal sinus disease, reflecting activation of convergent inflammatory pathways. Therapeutic decision-making is challenging because of the absence of specific guidelines and approved treatments. This review aimed to evaluate the efficacy and safety of advanced therapies—including biologic agents and small-molecule inhibitors—in DCS. In addition, therapeutic recommendations for disease management based on the available literature are proposed.</p> Methods <p>A systematic review was performed to identify original studies, case series, and case reports reporting outcomes of tumor necrosis factor alpha antagonists (TNFα), interleukin (IL)-12/23, IL-17, IL-23 inhibitors, or small-molecule agents in DCS.</p> Results <p>Forty-six studies comprising 125 patients were analyzed. TNFα inhibitors were the most frequently used therapies and demonstrated overall response rates exceeding 80%. Adalimumab and infliximab were the most commonly reported agents. IL-17 and IL-23 inhibitors yielded encouraging results in refractory disease, whereas JAK inhibitors emerged as alternative options. The adverse event (AE) rate was 8.3%, predominantly mild or moderate.</p> Conclusions <p>Advanced therapies—particularly TNFα inhibitors—appear effective and well tolerated for severe or refractory DCS. Earlier initiation of treatment may help modify the inflammatory disease course and potentially prevent irreversible scarring alopecia; however, this proposed benefit remains hypothesis-generating and warrants prospective validation.</p>