The degradation of creep resistance in Nickel-based single crystal superalloys is essentially ascribed to their microstructure evolution. Yet there is a lack of work that manages to simulate the effect of alloying element concentrations on microstructure degradation. In this research, a computational model is developed to connect the rafting kinetics of Ni superalloys with their chemical composition, by combining thermodynamics calculation and an energy-based microstructure model. The isotropic coarsening rate and γ/γ misfit stresses have been selected as composition related parameter, and the effect of service temperature, time and applied stress are also taken into consideration to simulate the evolutions of microstructure parameters during creep process. The different generations of commercial Ni superalloys are selected and their chemical compositions are calculated based on this model. The simulated microstructure parameters are validated by the results from experimental results and the existing analytical model. The capability of the model in predicting the microstructure characteristics may provide instructional thought in developing a novel computational guided design approach in Ni superalloys.