Psoriasis is a complex autoimmune disorder characterized by skin inflammation with keratinocyte proliferation, and 85% of cases present as plaque-type psoriasis. Biologics such as ustekinumab (UST) are highly successful therapies for psoriasis. To achieve maximum clinical efficacy while minimizing undesirable effects, therapeutic drug monitoring (TDM) for biologics has emerged. This study aims to measure the UST trough level (TL) and anti-drug antibodies (ADAs) and to evaluate clinical response in Iraqi patients with moderate-to-severe psoriasis in order to make appropriate recommendations for modifying therapy. This cross-sectional study enrolled 75 patients, divided into two groups: Group 1, patients who achieved the UST target TL (≥0.6 µg/mL); and Group 2, patients who did not achieve the UST target TL (<0.6 µg/mL). Significant differences were found in Psoriasis Area and Severity Index scores (P = 0.001) and body surface area involvement (P = 0.003), with Group 1 demonstrating lower values, indicating lower disease severity. No significant difference in ADA concentration was found between groups, and only two patients tested positive in Group 2. Based on the USTTL, ADAs, and clinical response, recommendations included dose escalation or shortening of the dosing interval for 29 patients, continuation of therapy for 34 patients, or switching to an alternative biologic agent for 12 patients. These findings reinforce the value of TDM in guiding personalized treatment decisions and highlight the clinical utility of integrating TL and ADA assessments into real-world practice.