Simulation-based design optimization and finite element method are used in this research to investigate weight reduction of car body structures made of metallic and composite materials under different design criteria. Besides crashworthiness in full frontal, offset frontal, and side impact scenarios, vibration frequencies, static stiffness, and joint rigidity are also considered. Energy absorption at the component level is used to study the effectiveness of carbon fiber reinforced polymer (CFRP) composite material with consideration of different failure criteria. A global-local design strategy is introduced and applied to multi-objective optimization of car body structures with CFRP components. Multiple example problems involving the analysis of full-vehicle crash and body-in-white models are used to examine the effect of material substitution and the choice of design criteria on weight reduction. The results of this study show that car body structures that are optimized for crashworthiness alone may not meet the vibration criterion. Moreover, optimized car body structures with CFRP components can be lighter with superior crashworthiness than the baseline and optimized metallic structures.