Psoriasis and spondyloarthritis (SpA), including psoriatic arthritis (PsA), are immune-mediated inflammatory conditions that affect the skin and musculoskeletal system. Males and female patients with psoriatic disease and SpA exhibit differences in clinical presentation, disease progression, and treatment response. The underlying biological mechanisms driving these sex differences remain poorly understood. This review explores the current evidence on sex-related differences in biomarkers and biological pathways in psoriasis, PsA, and SpA. While no conclusive sex-specific biomarkers have been validated, this review highlights several sex-related differences in biomarkers and biological pathways, including differences in bone turnover markers, IL-23/IL-17 pathway activity, pro-inflammatory cytokines, and cardio-metabolic profiles that may partially contribute to the clinical differences observed between male and female patients. Sex hormones may contribute to the altered bone metabolism and immune regulation in females. To effectively identify and validate sex-specific biomarkers, there is a need to prioritize sex as a biological variable in future research. Adopting such an approach should enhance more personalized therapeutic strategies and improve management for male and female patients with psoriatic disease and SpA.