The purpose of the present research was to compare the skin permeation and study the antifungal efficacy of Terbinafine hydrochloride (TH) transfersome, menthosome and ethosome formulations under non-occlusive conditions. Terbinafine hydrochloride is an antifungal drug for onychomycosis. Poor permeability of its external preparation leads to poor curative effect. Preparation of TH transfersome utilized the mixture component model to determine the optimized desirable formula using different concentrations of nonionic surfactant, Span and Tween (X1 & X2 respectively) were investigated. The results revealed that both X1 and X2 had a pronounced effect on vesicle size (Y1) and entrapment efficiency (EE) of the drug (Y2). The vesicles were prepared and characterized for shape, size, zeta potential and entrapment efficiency. Ex vivo study via Franz diffusion cells was used for the percutaneous absorption studies. The optimum desirable formula of transfersome, menthosome and ethosome formulations were showed vesicle size (78.7, 122.8 and 67.8 nm), zeta potential (-8.28, 8.77 and 11.30 mV) and encapsulation efficiency (92.67, 93.86 and 95.75%), respectively. Ex vivo permeation of the drug-loaded nanovesicle showed more than two to three folds higher permeation rate compared with drug suspension. Deformability verified elasticity of the preparation. Finally, TH nanovesicle formulations improved drug delivery with greater improvement in skin permeation and antifungal activity. Our selected formulae showed potent antifungal effect against Aspergillus niger for the treatment of fingernails or toenails.