Psoriasis is a chronic immune-mediated disease driven by interacting pro-inflammatory, angiogenic, and regulatory cytokine pathways. While individual cytokines of the IL-23/Th17 and Th1 axes have been widely studied, less is known about how multiple mediators behave collectively in relation to clinical severity. This study evaluated the integrated serum profile of IL-17A, IL-22, TNF-α, VEGF-A, IL-12(p40), and IL-10 in 34 patients with chronic plaque psoriasis and 19 matched healthy controls, and examined their associations with the Psoriasis Area and Severity Index (PASI). Psoriasis patients showed significantly elevated IL-17A, IL-22, TNF-α, VEGF-A, and IL-12(p40), whereas IL-10 displayed inverse pattern. Hierarchical clustering revealed a tightly interconnected pro-inflammatory cytokine network in untreated patients, with IL-17A, IL-22, and TNF-α forming a core synergistic cluster strongly associated with PASI. Systemic therapy reduced PASI and significantly decreased IL-17A, IL-22, IL-12(p40), and VEGF-A, accompanied by partial normalization of cytokine correlations. ROC analysis identified IL-22 and IL-12(p40) as potential biomarkers of treatment response. These findings demonstrate that psoriasis severity reflects coordinated activity across multiple immune pathways. Integrated cytokine profiling offers a more comprehensive understanding of disease biology and may support development of multi-marker tools for monitoring disease activity and guiding personalized therapy.