Psoriatic arthritis (PsA) is a heterogeneous, chronic inflammatory disease that primarily affects the joints and skin, presenting with variable clinical outcomes. This review explores sex-related differences in PsA, emphasizing clinical implications, radiological manifestations, comorbidities, and tailored treatments. By examining these sex-based differences, the review aims to provide insights into how clinicians can adjust treatment strategies to better meet the distinct needs of male and female patients. A systematic review was conducted across national registries, interventional and observational studies, and meta-analyses including adults (≥18 years) diagnosed with PsA. The review focused on comparing clinical and radiological features, comorbidities, and treatment outcomes between sexes. A comprehensive literature search was performed in PubMed, the Cochrane Library, and Embase on 12 January 2025, with a final update on 4 April 2025. Out of 80 records identified, 26 studies met the inclusion criteria. Women more frequently presented peripheral arthritis, reported higher pain levels, and exhibited greater functional impairment. In contrast, men showed a higher prevalence of axial involvement, radiographic progression, and more severe skin disease. Overall, treatment responses were less favorable in women, particularly with tumor necrosis factor inhibitors (TNFi), as reflected by lower rates of achieving low disease activity and reduced treatment persistence. In terms of comorbidities, data on cardiovascular risk factors were inconsistent across sexes, while depression and fibromyalgia were more frequently reported in women. Marked sex differences exist in the clinical profile, therapeutic response, and comorbidity patterns of PsA patients. Recognizing and addressing these disparities is crucial for tailoring personalized treatment strategies and optimizing patient outcomes.