The article reviews new and emerging oral and topical small-molecule treatments for psoriasis, focusing on their efficacy and safety. Psoriasis is a chronic inflammatory disease with a global prevalence of 1–3%, associated with significant health-related quality of life impairment. Biologic therapies have improved treatment outcomes for moderate-to-severe psoriasis, but oral treatments are preferred by many patients due to convenience. Current research is exploring oral and topical therapies with improved efficacy and safety, such as deucravacitinib, the first oral allosteric Tyk2 inhibitor approved for psoriasis. Targeted topical molecules, including AhR modulators and PDE-4 inhibitors, have also shown favorable outcomes. The review highlights various oral and topical treatments, including Jak inhibitors, TNF inhibitors, IL-17 inhibitors, IL-23 inhibitors, RORγT inhibitors, S1PR inhibitors, A3AR agonists, HSP90 inhibitors, and ROCK2 inhibitors. Jak inhibitors, such as tofacitinib, abrocitinib, baricitinib, peficitinib, solcitinib, itacitinib adipate, brepocitinib, ropsacitinib, and deucravacitinib, have shown efficacy in psoriasis treatment, with varying safety profiles. Deucravacitinib, an oral Tyk2 inhibitor, has been approved by the FDA and EMA for moderate-to-severe psoriasis. Other oral PDE4 inhibitors, such as apremilast and orismilast, have also demonstrated efficacy. Oral TNF inhibitors, like SAR441566, and IL-17 inhibitors, such as DC-806, are under investigation. Oral IL-23 inhibitors, including JNJ-77242113, have shown promising results in clinical trials. RORγT inhibitors, such as JTE-451 and AUR101, are also being evaluated. Sphingosine-1-phosphate receptor 1 antagonists, like ponesimod, are under development. The review emphasizes the importance of ongoing research to improve treatment options for psoriasis, focusing on safety, efficacy, and patient convenience.The article reviews new and emerging oral and topical small-molecule treatments for psoriasis, focusing on their efficacy and safety. Psoriasis is a chronic inflammatory disease with a global prevalence of 1–3%, associated with significant health-related quality of life impairment. Biologic therapies have improved treatment outcomes for moderate-to-severe psoriasis, but oral treatments are preferred by many patients due to convenience. Current research is exploring oral and topical therapies with improved efficacy and safety, such as deucravacitinib, the first oral allosteric Tyk2 inhibitor approved for psoriasis. Targeted topical molecules, including AhR modulators and PDE-4 inhibitors, have also shown favorable outcomes. The review highlights various oral and topical treatments, including Jak inhibitors, TNF inhibitors, IL-17 inhibitors, IL-23 inhibitors, RORγT inhibitors, S1PR inhibitors, A3AR agonists, HSP90 inhibitors, and ROCK2 inhibitors. Jak inhibitors, such as tofacitinib, abrocitinib, baricitinib, peficitinib, solcitinib, itacitinib adipate, brepocitinib, ropsacitinib, and deucravacitinib, have shown efficacy in psoriasis treatment, with varying safety profiles. Deucravacitinib, an oral Tyk2 inhibitor, has been approved by the FDA and EMA for moderate-to-severe psoriasis. Other oral PDE4 inhibitors, such as apremilast and orismilast, have also demonstrated efficacy. Oral TNF inhibitors, like SAR441566, and IL-17 inhibitors, such as DC-806, are under investigation. Oral IL-23 inhibitors, including JNJ-77242113, have shown promising results in clinical trials. RORγT inhibitors, such as JTE-451 and AUR101, are also being evaluated. Sphingosine-1-phosphate receptor 1 antagonists, like ponesimod, are under development. The review emphasizes the importance of ongoing research to improve treatment options for psoriasis, focusing on safety, efficacy, and patient convenience.