Based on simulation technology, the injection molding process of a glass fiber reinforced thermal management system substrate was simulated to evaluate the feasibility and optimize the scheme. By analyzing the filling resistance and gate matching results, the best glue feeding scheme was determined. According to the initial process calculation, the deformation range of the positioning hole of the substrate is 0.538 4 mm, which can not meet the design requirements. An orthogonal test was designed and analyzed with injection time, holding time, cavity temperature, and melt temperature as variables. The results show that the influence of holding time and injection time is extremely significant. The influence of cavity temperature is significant, but the influence of melt temperature is not significant. The optimized process parameters is A₂B₂C₁D₃. The simulation results of optimized process show that the deformation range of the positioning hole is 0.452 8 mm, which decreases by 15.9% and meets the design requirements, filling in good condition, without defects, notes and detention. The appearance of the actual sample pattern is good, and the deformation results are uniform, which verifies the correctness of the optimized process.