Motivated by a combination of increasing consumer demand for fuel efficient vehicles, more stringent greenhouse gas, and anticipated future Corporate Average Fuel Economy (CAFE) standards, automotive manufacturers are working to innovate in all areas of vehicle design to improve fuel efficiency. In addition to improving aerodynamics, enhancing internal combustion engines and transmission technologies, and developing alternative fuel vehicles, reducing vehicle weight by using lighter materials and/or higher strength materials has been identified as one of the strategies in future vehicle development. Weight reduction in vehicle components, subsystems and systems not only reduces the energy needed to overcome inertia forces but also triggers additional mass reduction elsewhere and enables mass reduction in full vehicle levels. Mass reduction can be achieved by removing materials that are not needed, substituting materials for those with lower density and/or higher strength, changing vehicle components and/or architectures to those require less material, or combinations of the above. New manufacturing and joining technologies and vehicle assembly processes as well as the associated simulation methodologies and tools also need to be developed in order to shift from current steel-intensive vehicles to lighter-weight vehicles with dissimilar materials, such as new generation advanced high strength steels, aluminum, magnesium, and composites.In this paper, computer simulations and design optimizations conducted to develop an aluminum-intensive body-on-frame vehicle with improved fuel economy and enhanced crashworthiness are presented. The modeling of a body-on-frame vehicle is more difficult than that of a traditional unitized vehicle due to the challenges associated with components such as body mounts and ladder frame structures that are not part of unitized vehicle construction. In addition, material database and constitutive laws representing the mechanical properties of new high strength aluminum alloys and different joining methods utilized in the aluminum-intensive vehicle needed to be established. The models of the vehicle's aluminum-intensive bodies and cargo beds, high strength steel ladder frames, body mounts, and joining methods were developed based on material coupon and component tests. To minimize vehicle weight for improved fuel economy and to optimize the vehicle crash pulse and intrusion simultaneously for enhanced crashworthiness, design optimizations of geometry, shape, material, thickness, and joining method were conducted for major components in crash zones. Extensive full vehicle computer simulations with different frontal impact conditions and various vehicle configurations were performed during the design phase not only to enhance crash performance for federal safety regulations and internal requirements but also to meet manufacturing constraints.