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Introduction: Psoriasis is a chronic immune-mediated disease that can be challenging to treat, especially in patients with severe disease or high body weight. Tildrakizumab is a monoclonal antibody which inhibits IL-23, approved for moderate-to-severe psoriasis with a standard 100 mg dose. A 200 mg dose may provide greater efficacy for patients over 90 kg or with high disease burden. Methods: This multicenter, prospective study evaluated the effectiveness and safety of tildrakizumab 200 mg in patients with moderate-to-severe psoriasis, focusing on those with specific challenges: body weight over 90 kg, baseline PASI ≥20, and difficult-to-treat areas. The study also compared bio-naive versus bio-experienced and male versus female patients. Adults received tildrakizumab 200 mg subcutaneously at weeks 0 and 4, then every 12 weeks. Results: Clinical improvements were assessed using PASI, DLQI, genital PASI, and NAPSI scores. After 24 weeks, the mean PASI score dropped from 14.6 to 0.4, with PASI 90 and PASI 100 scores exceeding 80% (100.0% and 80.3%, respectively). DLQI scores improved from 14.2 to 1.8, and significant improvements were seen in genital PASI and NAPSI scores. No significant adverse events occurred. Conclusions: Tildrakizumab 200 has been shown to be an effective therapeutic option, particularly for patients with high body weight, significant disease burden, and involvement of sensitive areas with no new safety signals. [ABSTRACT FROM AUTHOR]