Summary: A methodology has been developed to take advantage of hypersonic aircraft design characteristics to allow design optimizations using computational fluid dynamics and genetic algorithms. This methodology highlights the inherent advantages obtained from decoupling and then adding via explicit formulations, the viscous, thermal, species-transport and combustion physics into the implicitly solved Euler formulations of fluid flow. The resulting formulation is found to be robust and less sensitive to volume mesh refinement, thereby making it possible to use an automated mesh generation process. The mesh generator also takes advantage of the inherent two-dimensionality of the fluid flow around hypersonic aircraft and uses block-structured rhombohedrum meshes that are easy to control using an optimizer. A sample case study is presented in the form of the X-43 hypersonic aircraft which is then optimized for a Mach 6.5 flight using this new methodology.