AbstractWhen projecting and building new industrial facilities, getting integrated design alternatives and maintenance strategies are of critical importance to achieve the physical assets optimal performance, which is needed to be competitive in the actual global markets. Coupling Evolutionary Algorithms with Discrete Event Simulation has been explored both in relation to systems design and their maintenance strategy. However, it was not simultaneously considered when both the corrective and the preventive maintenance—consisting of achieving the optimum period of time to carry out a preventive maintenance activity—are taken into account before being considered by the authors of the present paper. This work couples Multi-objective Evolutionary Algorithms with Discrete Event Simulation in order to enhance the knowledge and efficiency of the methodology presented, which consists of exploring and optimizing simultaneously systems design alternatives and their preventive maintenance strategies. The aim consists of finding the best set of non-dominated solutions by using the system availability (first maximized objective function) with taking into consideration associated operational cost (second minimized objective function), while automatically selecting the system devices. Each solution proposed by the Multi-Objective Evolutionary Algorithm is analyzed by using Discrete Event Simulation in a procedure that looks at the effect of including periodic preventive maintenance activities all along the mission time. An industrial application case study is solved, and a comparison of the performance of five state-of-the-art and three more recently developed Multi-objective Evolutionary Algorithms is handled; moreover, the gap in the literature reviewed about the analysis regarding the effect of the discrete event simulation sampling size is faced with useful insights about the synergies of Multi-objective Evolutionary Algorithms and Discrete Event Simulation. Finally, the methodology is expanded to more complex systems which are successfully solved.