The introduction of biologic therapies has significantly improved the management of moderate-to-severe psoriasis, but subcutaneous administration can be inconvenient for some patients. This review focuses on the latest oral and topical therapies for psoriasis, particularly those under evaluation or development. Oral therapies include Jak inhibitors, TNF inhibitors, IL-17 inhibitors, IL-23 inhibitors, RORγT inhibitors, S1PR inhibitors, A3AR agonists, HSP90 inhibitors, and ROCK2 inhibitors. Topical therapies include AhR modulators, PDE-4 inhibitors, and retinoid-related orphan receptors (ROR) inhibitors. The efficacy and safety of these treatments are discussed, highlighting the progress in understanding psoriasis pathogenesis and the development of targeted molecules. Key findings include the approval of decuravacitinib, an oral allosteric Tyk2 inhibitor, for moderate to severe psoriasis. Other promising oral and topical treatments, such as abrocitinib, baricitinib, peficitinib, solcitinib, itacitinib adipate, brepocitinib, ropsacitinib, deucravacitinib, BMS-986202, SAR-20347, zasocitinib, and VTX958, are also reviewed, along with their clinical trial results and ongoing research. The review emphasizes the importance of oral administration and the potential of these new therapies to improve patient convenience and treatment outcomes.The introduction of biologic therapies has significantly improved the management of moderate-to-severe psoriasis, but subcutaneous administration can be inconvenient for some patients. This review focuses on the latest oral and topical therapies for psoriasis, particularly those under evaluation or development. Oral therapies include Jak inhibitors, TNF inhibitors, IL-17 inhibitors, IL-23 inhibitors, RORγT inhibitors, S1PR inhibitors, A3AR agonists, HSP90 inhibitors, and ROCK2 inhibitors. Topical therapies include AhR modulators, PDE-4 inhibitors, and retinoid-related orphan receptors (ROR) inhibitors. The efficacy and safety of these treatments are discussed, highlighting the progress in understanding psoriasis pathogenesis and the development of targeted molecules. Key findings include the approval of decuravacitinib, an oral allosteric Tyk2 inhibitor, for moderate to severe psoriasis. Other promising oral and topical treatments, such as abrocitinib, baricitinib, peficitinib, solcitinib, itacitinib adipate, brepocitinib, ropsacitinib, deucravacitinib, BMS-986202, SAR-20347, zasocitinib, and VTX958, are also reviewed, along with their clinical trial results and ongoing research. The review emphasizes the importance of oral administration and the potential of these new therapies to improve patient convenience and treatment outcomes.