For high-speed railway carbody structure durability analysis problems in China, one integrated method based on MBS (multibody simulation) is proposed here. Firstly, one EMU (Electricity Multiple Unit) full vehicle was performed to dynamic modeling and simulation. The numerical simulation results were applied to illustrate the vehicle dynamic characteristics. And the relationships between structural strength, stiffness, and frequency characteristics were also studied. Secondly, the multidisciplinary design technique was used to solve multi-mode coupled vibration of carbody structure on the cumulative effects of local vibration and damage effects, as well as structure light-weighting and other parallel optimization problems. Finally, the effective measures were proposed to control carbody structure’s physical failure.