Psoriatic arthritis (PsA) is a chronic inflammatory disease with diverse clinical phenotypes, ranging from mild oligoarticular involvement to severe, erosive arthritis. Genetic predisposition, particularly human leukocyte antigen (HLA) alleles, plays a critical role in disease susceptibility and severity. A prospective cohort study was conducted at the State University of Medicine and Pharmacy “Nicolae Testemițanu” between 2007 and 2024, enrolling 357 PsA patients. Participants were stratified into early PsA (<3 years disease duration) and late PsA (>5 years). HLA typing was performed using PCR-SSO methods, and associations with disease subtypes were analyzed through logistic regression. A predictive model was developed to estimate the probability of PsA phenotypes based on HLA alleles. HLA-B27 was strongly associated with axial PsA (OR = 6.32, p < 0.001), while HLA-B16(38) and HLA-B38 were linked to polyarticular and distal interphalangeal PsA, particularly in patients with severe radiographic damage. HLA-B13 correlated with distal interphalangeal involvement, whereas HLA-B7 demonstrated a potential protective effect (OR = 0.51, p = 0.09). The predictive formula integrating HLA markers enhanced PsA classification accuracy, with a mean absolute error (MAE) of 0.287. Our findings underscore the clinical relevance of HLA genotyping in PsA stratification and its potential role in personalized medicine. The developed predictive model may refine diagnostic algorithms, such as CASPAR, improving early detection and risk stratification. Future research should investigate HLA class II alleles, epigenetic interactions, and environmental factors to further optimize predictive approaches.