The aim of this study was to design, formulate, and optimize a food-grade water-based saffron essential oil nanoemulsion for application in beverages and aqueous food products. To identify the optimal emulsifier and co-emulsifier combination, the effects of various emulsifiers (Tween 80, gum arabic, lecithin, whey protein, modified starch, Brij35, and Span 20) and co-emulsifiers (propylene glycol, glycerin, and ethanol) on initial stability and transparency were evaluated. The results showed that the combination of Tween 80 and propylene glycol was the most efficient emulsifying system. Subsequently, using response surface methodology with a central composite design, the effects of five independent factors (Tween 80 concentration, propylene glycol concentration, saffron essential oil concentration, ultrasonication power, and time) on droplet size, zeta potential, transparency, and initial stability were investigated. The optimal formulation consisted of 10% Tween 80, 9% propylene glycol, and 3.5% saffron essential oil, produced under ultrasonication conditions of 360 W power for 150 s. The optimized nanoemulsion exhibited a mean droplet size of 14.7 nm, zeta potential of -45.18 mV, transparency of 93.1%, and initial stability of 100%. Accelerated stability tests (4 weeks at 45°C and pasteurization at 75°C for 15 min) demonstrated excellent physical and optical stability. GC-MS analysis confirmed the presence of 29.52% safranal in the final nanoemulsion. Sensory evaluation using the Hedonic scale revealed that the nanoemulsion had significantly superior odor, taste, and overall acceptability compared to non-emulsified saffron essential oil. Furthermore, the nanoemulsion maintained complete physical stability under freeze-thaw cycles (-18°C), extreme pH conditions (2 and 9), and in the presence of electrolyte (200 mM NaCl). This study demonstrated that systematic optimization of formulation and process parameters can produce a saffron nanoemulsion with ultrafine droplets, exceptional transparency, and superior physicochemical and sensory stability, offering great potential for widespread application in the food industry, particularly in clear beverage production.