Aim: This study aimed to employ a Quality by design (QbD) based approach for the development and optimization of stable voriconazole (VCZ) nanoemulsion (NE). Materials and Methods: The NE was developed using Tween 80 as a surfactant, PEG 400 as a cosurfactant and sesame as oil phase. The Design of the Experiment (DoE) consisted Central composite design for the optimization. The independent variables were the concentration of surfactant mix (Smix), oil phase and RPM while globule size, zeta potential and polydispersity index (PDI) were the dependent variables. The NE was evaluated for particle size, zeta potential, pH, viscosity, transmittance, drug content, in-vitro drug release, and stability studies. Results: The optimized formulation showed an approximate globule size of 34.39 nm, zeta potential of 63.62 and polydispersity index of 0.27 and was stable for three months at room temperature. in vitro. Conclusion: A QbD-based approach can aid in the development of robust and thermodynamically stable NEs.