Objective: This study aims to formulate a ketoconazole patch containing electrospun nanofibres and enhance the solubility due to theincreased particle surface using the electrospinning method. Methods: The Design-Expert version13 software was used in experimental designing, to ensure an efficient nanofiber preparation process. Several nanofiber formulations were prepared with different concentrations of drug and polymers. In this study, Ketoconazole was selected as the model drug, ketoconazole is widely used as an antifungal drug in the treatment of fungal infections. Eudragit and Polyethylene glycol polymers were used with ketoconazole to formulate electrospun nanofibers. Then Ketoconazole nanofibers were investigated and evaluated chemically and morphologically by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Results: Utilizing the electrospinning method, Ketoconazole electrospun nanofiber was successfully fabricated. The producedketoconazole-loaded nanofibers mat was formulated as a dermal patch. The Eudragit and polyethylene glycol polymers revealed goodcharacteristics that led to the production of uniform ketoconazole nanofibers. The prepared patch showed good physical and mechanicalproperties. The SEM results Images for the produced nanofiber mat showed good nanofiber distribution and no beads formation withseveral fiber diameter sizes, while Fourier Transform Infrared Spectroscopy findings revealed the conjugation between polymers andketoconazole pure powder, the major characteristic peaks of ketoconazole appeared in the FTIR spectrum. Formula 7 showed minimumnanofibers diameter with maximum entrapment efficiency. Conclusions: In this study, the use of the electrospinning method completed the formulation of a dermal patch containing antifungalnanofibers successfully. Using design expert software to ensure maximum optimization, two biocompatible polymers were used, Eudragit E100 and PEG 600 to formulate ketoconazole nanofibers. The formulated dermal patch could be promising for pharmaceutical antifungal applications.