We report on an analysis of the parameters that control both the stability and tunability of O/W nanoemulsions prepared by the phase inversion composition (PIC). These nanoemulsions are prepared with Tween 80 and Span 80, two nonionic surfactants, that can be mixed to adjust the hydrophilic lipophilic balance (HLB). We used a process mixture design method, which combines mixture and process design with phase diagrams, to describe the cross-link between parameters like composition, temperature of preparation, and HLB. Nanoemulsions, stable for several days, are obtained by this method, and they remain unchanged even at high concentration. We have identified the different critical distances of interactions that control the degree of freedom in the motion of the oil droplets. The diameter of these oil droplets could be adjusted between 50 and 300 nm. Different parameters, among them the temperature of preparation, the surfactant over oil ratio (S/O), and the HLB, allow control the final size of the nanoemulsions. As these parameters can exhibit opposite effects on the droplet size, the process mixture design method allowed us to illustrate these cross-interactions.