Occupant safety is a top priority of military vehicle designers. Recent trends have shifted safety emphasis from the threats of ballistics and missiles toward those of underbody explosives. For example, the MRAP vehicle is increasingly replacing the HMMWV, but it is much heavier and consumes twice as much fuel as its predecessor. Recent reports have shown that fuel consumption directly impacts personnel safety; a significant percentage of fuel convoys that supply current field operations experience casualties en route. While heavier vehicles tend to fare better for safety in blast situations, they contribute to casualties elsewhere by requiring more fuel convoys. This study develops an optimization framework that uses physics-based simulations of vehicle blast events and empirical fuel consumption data to calculate and minimize combined total expected injuries from blast events and fuel convoys. Results are presented by means of two parametric studies, and the utility of the framework is discussed in a dynamic context and for evaluating casualty-reduction strategies.