Dolutegravir Sodium is a potent antiretroviral medication used in the treatment of HIV. It is BCS Class II compound and is practically insoluble at normal gastric pH range. The research aimed to discover and optimize operational and formulation factors that affect the characteristics of the drug. 32 factorial design was utilized for the investigation. PVP K30, Polyvinyl Alcohol, Polxammer 407, and Polxammer 188 were used in preparation of nanosupension. The formulation variables tested were the polymer concentration, whereas the manufacturing variable was homogenization speed. Particle size and saturation solubility were two responses that were assessed in this investigation. The results of the analysis of variance show that the polymer concentration and homogenization speed significantly impact the saturation solubility and particle size of the nanosuspension. The contour plot and resulting polynomial formula assist in estimating the values of chosen independent factors to develop the best nanosuspension formulations with the required characteristics.