This paper presents a method to optimize an oil tanker cargo hold’s structural scantlings based on stiffened panel ultimate limit states. Two different tanker models and their results are presented demonstrating this optimization procedure using models of varying mesh densities. The full ship finite element models are loaded with multiple load cases, design bending moments, external hydrostatic pressure, and internal tank pressure. The working stresses of a stiffened panel, which are used for the panel’s ultimate limit states assessment, are obtained by 3D finite element analysis. Each stiffened panel is then optimized using multi-objective genetic algorithms for its weight and safety. The optimization process is performed on two different versions of the same vessel: one with all stiffeners defined explicitly and one with internal stiffeners (allowing the stiffener layout to be changed during the optimization). The numerical results show that the proposed method is very useful to perform ultimate strength based ship structural optimization with multiple objectives, namely minimizing the structural weight and maximizing structural safety.