The underwater explosions due to an accident or other potential reasons cause severe shocks in the fluid medium. Safety assessment is an essential design requirement where the blast load concentration is expected due to smaller standoff distances. In the present work, the probabilistic analysis of structural response due to the underwater explosion is studied using NESSUS software. The study helps improve the concepts of improved blast mitigation strategies. The shock loading considered varies spatially and temporally. The fluid pressure is transformed into structural nodal forces. Taylor’s plate theory is used to estimate the shock loading. In the analysis, the material is considered to be rate-dependent elastoplastic with temperature softening. Maximum central deflection against shock factors is obtained to arrive at the safe thickness of the stiffened and unstiffened plates for the optimum design characteristics using LS-DYNA software. The finite element approach adopted efficiently captures expected failures for various combinations of structural properties leading to an optimized design to withstand the target explosion. Johnson-Cook dynamic failure model is employed as a limit state function for reliability assessment. Sensitivity analysis enables to achieve target reliability.