Multi-disciplinary design optimisation based on rigid-flexible multi-body system (MBS) is presented to solve the multi-object design optimisation problems of lightweight carbody structure by considering the fluid-structure interactions at different typical load cases. A mathematical model is developed to simulate structure interactions based on the theory of finite elements. The model is integrated with a multi-object optimisation approach which utilises the Non-Sort Genetic Algorithm method. The MBS was used to understand complex vehicle system dynamics performance and obtain the structure load time histories. Through performing structural quasi-static stress analysis method, the structure dynamic stress/strain histories were obtained for fatigue life evaluation. The obtained results demonstrate the effectiveness of the proposed approach in simultaneously considering the structural vibration and the aerodynamic pressure at several vehicle speeds by proper lightweight design. This method has the advantage which can be used to understand the interaction mechanism between the vehicle dynamics characteristic and lightweight structural fatigue damage.