Purpose: Topical nanoemulsion comprising of fluconazole and curcumin was developed to target multiple drug resistance dermatophytes infection and to facilitate cutaneous delivery of these poorly water soluble drugs. Methods: Almond oil, sesame oil and paraffin light were used to formulate nanoemulsions and screened for the stability. The solubility of fluconazole and curcumin in surfactants, co-surfactants and oils was screened to decide the various components of the nanoemulsion. The oil phase was light paraffin whereas tween 80 and span 80 were the surfactants and ethanol was used as a co-surfactant. To identify the area of nanoemulsion existence, a pseudoternary diagram was drawn and optimum systems were developed. Drug-loading efficiency was assessed and the developed nanoemulsions were characterized for globule size, stability, robustness to dilution and pH. The optimized nanoemulsion was further evaluated for drug content, viscosity, skin permeation study (ex vivo) and assay of antifungal activity. Results: The globule size was below 200 nm and uniform for the optimized nanoemulsion formulation. It showed enhanced skin permeation (ex vivo) and better antifungal efficacy as compared to the native form of fluconazole and curcumin suspensions. Antimicrobial assay confirmed the synergistic effect of fluconazole and curcumin combination against multiple drug resistance Trychophytum rubrum and Trichophyton metagrophytes as compared to the fluconazole alone. Conclusion: The results clearly indicate an optimized delivery of fluconazole and curcumin in a synergistic way from the nanoemulsion formulation. This resulted in better penetration of these poorly soluble molecules and overall enhanced antifungal activity as compared to these drugs as such against multiple drug resistance dermatophytes.