This chapter introduces the approach to ab initio calculate the values based on computational methods, and a Figure of Merit to predict the microstructure stability of bulk heterojunction (BHJ) composites. It focuses on solute–liquid miscibility and solute–solute miscibility and explains the degradation mechanisms related to microstructure. The chapter provides a detailed insight into the theoretical, computational and experimental principles of mixing of organic semiconductors. The microstructure of a BHJ film is determined by the competition between thermodynamics and kinetics during the drying process. The chapter describes the M. L. Hansen solubility parameters (HSPs) can be visualized in a three dimensional coordinates system with the solubility parameters as axes. The mixing compatibility of a polymer and a fullerene is graphically represented by the values of thermodynamic variables when the equilibrium is established among the phases of a system.