<p>Psoriasis, a chronic inflammatory skin disorder, presents challenges in drug delivery due to the skin’s barrier properties, necessitating advanced systems for efficient treatment. Ethosomes and transfersomes, vesicular carriers developed to enhance transdermal drug delivery, have shown significant promise in managing psoriasis. Ethosomes, composed of phospholipids and ethanol, enhance drug permeation by increasing the fluidity of the stratum corneum and interacting synergistically with skin lipids. Transfersomes, composed of phospholipids and surfactants, exhibit deformability, allowing them to squeeze through skin pores for deeper penetration. Studies demonstrate that both systems improve the bioavailability of drugs like methotrexate and Cyclosporine A (CyA), which are traditionally limited by poor skin absorption. Ethosomes, with their high ethanol content, offer superior skin permeability over transfersomes and liposomes, making them ideal for delivering high molecular weight drugs like CyA. Comparative studies have shown ethosomes to achieve greater drug retention and permeation, leading to improved therapeutic outcomes in psoriasis models. Transfersomes excel in drug deposition within the skin, making them suitable for localized treatment. Recent advancements in ethosomal formulations, such as incorporating salicylic acid and novel agents like thymoquinone, further enhance their therapeutic potential in psoriasis. This review explores the mechanisms, formulations, and comparative effectiveness of ethosomes and transfersomes in psoriasis treatment. Despite the promising results, further studies are necessary to optimize their clinical application and fully understand their drug delivery mechanisms. Ethosomes and transfersomes represent a significant step in psoriasis management through improved transdermal drug delivery.</p>