Combining substructure and power flow theory, in this paper an external program is written to control MSC. Nastran solution process and the substructure frequency response are also formulated accordingly. Based on a simple vehicle model, characteristics of vibration, noise, and power flow are studied, respectively. After being compared with the result of conventional FEM (finite element method), the new method is confirmed to be feasible. When it comes to a vehicle with the problem of low-frequency noise, finite element models of substructures for vehicle body and chassis are established, respectively. In addition, substructure power flow method is also employed to examine the transfer characteristics of multidimensional vibration energy for the whole vehicle system. By virtue of the adjustment stiffness of drive shaft support and bushes at rear suspension lower arm, the vehicle interior noise is decreased by about 3 dB when the engine speed is near 1050 rpm and 1650 rpm in experiment. At the same time, this method can increase the computation efficiency by 78%, 38%, and 98% when it comes to the optimization of chassis structure, body structure, and vibration isolation components, respectively.