Twin-screw extrusion is used to compound fillers into a polymer matrix in order to improve the properties of the final product. The resultant properties of the composite are determined by the operating conditions used during extrusion processing. Changes in the operating conditions affect the physics of the melt flow, inducing unique composite properties. In the following work, the Residence Stress Distribution methodology has been applied to model both the stress behavior and the property response of a twin-screw compounding process as a function of the operating conditions. The compounding of a pigment into a polymer melt has been investigated to determine the effect of stress on the degree of mixing, which will affect the properties of the composite. In addition, the pharmaceutical properties resulting from the compounding of an active pharmaceutical ingredient are modeled as a function of the operating conditions, indicating the physical behavior inducing the property responses.