To mitigate the risk of manufacturing defects and improve the efficiency of the autoclave-processed thick composite component curing process, parameter sensitivity analysis and optimization of the curing profile were conducted using a finite element model, Sobol sensitivity analysis, and the multi-objective optimization method. The FE model based on the heat transfer and cure kinetics modules was developed by the user subroutine in ABAQUS and validated by experimental data. The effects of thickness, stacking sequence, and mold material on the maximum temperature (Tmax), temperature gradient (ΔT), and degree of curing (DoC) were discussed. Next, parameter sensitivity was tested to identify critical curing process parameters that have significant effects onTmax,DoC, and curing time cycle (tcycle). A multi-objective optimization strategy was developed by combining the optimal Latin hypercube sampling, radial basis function (RBF), and non-dominated sorting genetic algorithm-II (NSGA-II) methods. The results showed that the established FE model could predict the temperature profile andDoCprofile accurately.Tmaxalways occurred in the mid-point regardless of laminate thickness; theTmaxandΔTincreased non-linearly with the increasing laminate thickness; but theDoCwas affected slightly by the laminate thickness. The stacking sequence has little influence on theTmax,ΔT, andDoCof laminate. The mold material mainly affected the uniformity of the temperature field. TheΔTof aluminum mold was the highest, followed by copper mold and invar steel mold.Tmaxandtcyclewere mainly affected by the dwell temperatureT2, andDoCwas mainly affected by dwell timedt1and dwell temperatureT1. The multi-objective optimized curing profile could reduce theTmaxandtcycleby 2.2% and 16.1%, respectively, and maintain the maximumDoCat 0.91. This work provides guidance on the practical design of cure profiles for thick composite parts.