In this paper, the underwater blast behavior of a multi-compartment protective system was numerically analyzed using AUTODYN. A group of structures composed of three circular metal plates and two cylindrical compartments in between were subjected to a contact underwater explosion (UNDEX). An experimental study was carried out to validate the numerical simulation model. Besides, a rigorous parametric study was conducted on structural geometry and its material variables using the full-factorial and response surface methods in DoE software. Later on, a multi-objective optimization was carried out on the obtained objective functions for the prediction of the Central Deflection of the backplate (CentD) and Energy Absorption per Areal Mass (EApM). The proposed optimal condition was also validated using the numerical simulation model. It was found that using the arrangement of Al2024-T3, St37, and St37 as the faceplate, midplate, and backplate in a configuration as well as mediums of water and air in-between outperforms in terms of minimum CentD and maximum EApM. Using the same mediums in compartments regardless of type of layers leads to backplate tearing and structure failure. From the structural geometry point of view, it was found that variations of midplate thickness and fore compartment height have the most influence on CentD and EApM, respectively. Therefore, the suggested configuration can be successfully used as a marine armor with dimensional considerations under contact underwater explosion.