The aim of this research was to study the effect of local raw materials on the formulation of a base cream formulation and determine the optimum proportion of each material that gives the required properties. Physicochemical properties of cream formulations can be affected by their viscosity, spreadability, and particle size. The quality of the base cream is directly linked to the basic material used in the formulation. Screening of independent factors, namely oil phase (sesame oil, soybean oil, and liquid paraffin), aqueous phase (Aloe vera gel, propylene glycol, and glycerol), and surfactant (soy lecithin, tween, and soy lecithin/tween) was done to choose the best raw material required for the preparation of the base cream. Based on the screening criteria, sesame oil, Aloe vera gel, and soy lecithin were chosen as the best local raw materials. Using a multi-response optimization, the mixing fractions of sesame oil, Aloe vera gel, and soy lecithin were found to be 24%, 28%, and 10%, respectively. This base cream can be used as a suitable matrix for formulation in the cosmetic and pharmaceutical industries.