To explore the influence of the non-uniformity of quenching temperature on large-sized thin-walled multi-chamber aluminum alloys, this study aims to investigate the influence patterns of process parameters and develop an optimization strategy. A numerical model of the quenching process was established based on the Workbench software platform to analyze the effects of quenching methods, the strength of the cooling zone, the nozzle spacing, and operating speed affect the temperature field during the quenching process. Subsequently, a response surface method was employed to perform multi-objective optimization of key process parameters. The research results show that the use of stepped quenching can improve the uniformity of the temperature field during the quenching of profiles and ensure the critical cooling rate in the sensitive area. As the cooling intensity of the strong cooling zone increases, the cooling rate of the profile increases, while the uniformity of the temperature field decreases. As the longitudinal nozzle spacing in the strong cooling zone increases, the temperature difference of the profile in the strong cooling zone decreases, and at the same time, the cooling rate of the profile also slows down. As the running speed of the profile increases, the cooling rate of the profile shows a trend of first rising and then falling. The response surface optimization method was adopted to explore the influence laws of the cooling intensity coefficient of the strong cooling zone, the running speed of the profile and the longitudinal nozzle spacing of the strong cooling zone on the cooling rate of the profile, and the optimal process parameters of the profile were obtained. The optimized scheme successfully reduced the quenching temperature difference and eliminated temperature recovery by employing an alternating cooling mode of mist and high-intensity jet cooling in the intensive cooling zone.