Cure process is the most crucial stage for manufacturing composite parts and final quality of the part is strongly dependent on the cure profile used in the curing process. In this paper, a novel approach based on cure simulation using finite element method and multi-objective genetic algorithm is developed to optimize cure profile for thick thermoset composites. Three objectives are considered simultaneously, which include the maximum difference in degree of cure, the maximum temperature difference, and the total cure time. Optimal Pareto front is obtained and the optimized cure profile is selected from Pareto front for the given application. A 24-mm thick unidirectional laminate is taken as an example and the results show that compared to typical cure profile, the optimized cure profile leads to approximately 56% reduction in the maximum difference in degree of cure, 71% decrease in the maximum difference in temperature during cure, and 33% reduction in the total cure time. It is also indicated that the residual stress can be remarkably decreased and the cure efficiency is significantly improved using the present method. The present method can also be applied to various geometries with various thicknesses and is able to provide an important reference for determination of cure profiles for the manufacturing of composite structures.