The main objective of this study is to present a methodology to model the microstructure and mechanical properties of ZE41-xCa-ySr alloys for integrated optimization calculation of the heat treatment process of gearbox casting. Firstly, the models of microstructure and mechanical properties of ZE41-xCa-ySr alloys (0 ≤ x ≤ 2, 0 ≤ y ≤ 0.2) are developed using an artificial neural network (ANN) and multivariate regression. The dataset for ANN and regression models is generated by investigating the microstructures and mechanical properties of the ZE41-xCa-ySr alloys. The inputs for ANN and regression models are Ca and Sr contents, aging temperature and aging time. The outputs are grain size, ultimate tensile strength, elongation and microhardness. The optimal ANN model is obtained by testing the performance of different network architectures. In addition, multivariate regression models have been built based on the Least Squares method. Secondly, based on SiPESC software, an Integrated Computing Platform is constructed by combining the scripting language with the command line operation of simulation software, realizing the “process—microstructure—property” optimization calculation. Finally, based on the developed regression model, an Integrated Computing Platform batch called MATLAB achieves the heat treatment process optimization based on mechanical property prediction. The optimum aging temperature of the ZE41-0.17Ca-0.2Sr alloy is 322 °C, and the corresponding aging time is 11 h. Furthermore, the optimized results are validated by the ANN model, suggesting that ANN predicted results are in good agreement with optimized results. As a consequence, this work provides a new strategy for the research and development of Mg alloys, contributing to acceleration in the development of magnesium alloys.