The onychomycosis treatment remains a big challenge for onychologist due to the shorter nail residence time of topical formulations and the lack of availability of novel formulations in markets for new generation antifungal drugs. The objective of this work was to design, develop, optimize, and evaluate microemulsion formulations for effective delivery of efinaconazole through transungual route in onychomycosis treatment. Capmul? MCM (Glyceryl Caprylate/Caprate) as oil, Labrasol? (caprylocaproyl polyoxyl-8 glycerides) as a surfactant, and Transcutol? P (diethylene glycol monoethyl ether) as co-surfactant exhibited higher solubility of efinaconazole and surfactant-cosurfactant mixture (Smix) in a ratio of 1:1 rendered higher microemulsion region in the pseudoternary phase diagram. The optimized microemulsion formulation containing 6%w/w oil phase, 22.5%w/w surfactant, 22.5%w/w co-surfactant, and 49%w/w demineralized water was converted into gel formulation using 1.0%w/w Carbopol? 934 P gelling agent and evaluated for stability of 6 months. The optimized microemulsion formulation globule size was less than 100 nm. The ex vivo permeation confirmed improved permeation of efinaconazole from microemulsion formulations (346.36?12.90?gcm? 2) in comparison to reference formulation without observing any lag in drug permeation through the nail plate. The in vitro antifungal study data indicated increased antifungal efficacy relative to efinaconazole topical solution against Trichophyton rubrum, Trichophyton mentagrophytes, and Candida albicans species. Further, an in vitro cell cytotoxicity study exhibited no toxic effect for any excipients used in the formulation while applied on nail cells. Hence, the efinaconazole loaded microemulsion formulations could be considered as an effective therapy in the treatment of onychomycosis.