Psoriasis is a chronic inflammatory disease that affects the skin and joints, with a worldwide prevalence of 2-3%. The management of psoriasis is individualized and may involve a combination of different treatment modalities. NB-UVB is a commonly used phototherapy, while MTX is an immunosuppressive drug with anti-proliferative and anti-inflammatory effects. TWEAK, a member of the TNF-ligand superfamily, plays a role in the pathogenesis of psoriasis by promoting the expression of proinflammatory mediators from various cell types. Studies have shown that NB-UVB and MTX can inhibit keratinocyte growth and downregulate the expression of cell adhesion molecules, which can moderately decrease systemic TWEAK levels in psoriasis patients. However, more research is needed to fully understand the role of TWEAK in psoriasis and its relation to different treatment methods. Therefore, this review article aims to discuss the role of TWEAK levels in NB-UVB phototherapy and MTX in the treatment of psoriasis.