(1) Background: The present study aimed to assess the antifungal effectiveness of a topical innovative formulation containing the association of an antifungal agent, voriconazole (VCZ), and the essential oil of Pinus sylvestris L. (PSEO). (2) Methods: Pseudo-ternary phase diagram and D-optimal mixture design approaches were applied for the development and the optimization of the o/w nanoemulsion. The optimized formulation (NE) was subjected to physicochemical characterization and to physical stability studies. In vitro permeation studies were carried out using the Franz cell diffusion system. The antimycotic efficacy against Microsporum canis was carried out in vitro. (3) Results: Optimal nanoemulsion showed great physical stability and was characterized by a small droplet size (19.015 nm ± 0.110 nm), a PDI of 0.146 ± 0.011, a zeta potential of −16.067 mV ± 1.833 mV, a percentage of transmittance of 95.352% ± 0.175%, and a pH of 5.64 ± 0.03. Furthermore, it exhibited a significant enhancement in apparent permeability coefficient (p < 0.05) compared to the VCZ free drug. Finally, NE presented the greatest antifungal activity against Microsporum canis in comparison with VCZ and PSEO tested alone. (4) Conclusions: These promising results suggest that this topical innovative formulation could be a good candidate to treat onychomycosis. Further ex vivo and clinical investigations are needed to support these findings.