This research introduces a novel methodology for optimizing the structural design of a full-scale hypersonic aircraft, integrating a multifaceted approach across different levels of modelling detail to enhance a variety of performance metrics. The proposed approach is capable of reduce the vehicle mass, while meeting the necessary operational requirements and maintaining an acceptable computational cost. The methodology, based on a coupled bi-level size optimization and denoted as single-objective bi-level optimization (SOBLO), is applied to the passenger cabin of the STRATOFLY MR3 hypersonic cruiser vehicle. This results in a substantial reduction in the baseline concept design weight, estimated to be more than half on average. The procedure is extended to incorporate a multi-objective optimization approach (MOBLO), which generates a Pareto frontier that provides significant information for selecting the optimal trade-off design, considering manufacturability constraints. The outcomes underscore the efficacy of the proposed methodology and highlight its usefulness in sizing complex aircraft configurations, particularly under the demanding loads imposed by a hypersonic flight regime. This approach has the potential to improve the overall production process and enable designers to attain feasible structural design solutions during early stages of development.