This work addresses a novel technique for selecting the best process parameters for the 4H–SiC epitaxial layer in a horizontal hot-wall chemical vapor reactor using a transient multi-physical (thermal-fluid-chemical) simulation model and combined with a machine-learning model. An experiment was performed to validate the feasibility of the numerical model. Secondly, a single-factor analysis was conducted to investigate the effects of process parameters, including the deposition temperature, inlet-flow volume, rotational speed of the susceptor, and cavity pressure, on the quality of the 4H–SiC epitaxial layer. Finally, a machine learning algorithm, the ant colony optimization-back propagation neural network (ACO–BPNN), was employed to develop the input/output model and optimize process parameters for obtaining a high-quality epitaxial layer and reducing the optimization cycle and costs. Notably, the optimized process was validated by real experiments, where the error between calculation and experiment is 4.03 % for deposition rate and 0.49 % for coefficient of variation, respectively. The results highlight the model as reliable and lay the foundation for the CVD growth of the 4H–SiC epitaxial layer.@en