The topical and transdermal routes of drug administration are long known to the field of pharmaceutics. These routes have been explored for the delivery of a wide range of therapeutic agents over centuries. However, the anatomy of the skin and the physicochemical properties of molecules limit their transport via these routes. Transferosomes are nanovesicles with different contents that play a role in various biological and pathological processes. It offers significant advantages over other delivery systems such as liposomes and polymeric nanoparticles. Although exosomes are expected to be effective therapeutic agents, their optimal use remains a challenge. The development of methods for large-scale production, isolation, and drug loading is necessary to improve their efficiency and therapeutic potential. The current challenges and potential directions of this new area of drug delivery that liposomal delivery of drugs was reported to be limited to the upper layers of skin. This led to the development of self-regulating and self-adaptable vesicles known as transferosomes. Among all the prepared formulations, one optimized formulation was chosen by the point prediction method and evaluated for drug-polymer compatibility, particle size, and surface charge analysis, followed by skin permeation and pharmacodynamic studies. The optimized transferosomal gel of ketoconazole showed all responses which confirm with the values predicted by the design. Results of the current study suggest that the development of such combinational delivery system can result in a rational therapeutic regimen for effective treatment of concomitant disease conditions of fungal disease patients. Keywords: Transferosome, Ketoconazole, Fungal disease, Gel, Vesicular system