Purpose The existing powertrain mounting system (PMS) design principles only assume uncoupled PMS as 6 degrees of freedom (DOF). This assumption ignores the dynamic interactions between PMS and other systems. To address this shortcoming, a coupled PMS and multi-driveline mounting system (MDMS) problem is formulated and investigated. Furthermore, design logic and simulation methods to optimize the PMS based on the vibration reduction contributed from the PMS in real vehicle operating conditions are proposed in this paper. Methods Firstly, the key events that occur in real vehicle operating conditions are formulated and described along with eigenvalues and mode energy criteria. Secondly, a multi-body dynamics simulation model of a vehicle with 16 DOF and 22 DOF problems is taken into consideration to design the PMS. This simulation model is validated with experimentally measured vibrations on the powertrain mount. Thirdly, the influence of MDMS on PMS vibration performance is analytically evaluated in terms of eigensolutions and frequency responses. Finally, a novel systematic and procedural analysis approach is proposed. This new approach treats the PMS and MDMS as coupled 12 DOF systems, which are modeled by considering the powertrain mass and its bushing stiffness proprieties; along with the multi-driveline masses, joints kinematics, and its bushing stiffness proprieties. This coupled system with the vehicle model forms a 22 DOF system and is used for rigid body modes (RBM) optimization analysis. Result and Conclusions The results demonstrate that the conventional approach achieves all design objectives during the early design stage as evident from the results of the 16 DOF case. However, the PMS isolation performance degrades when this model is applied to real vehicle operating events, as demonstrated by the 22 DOF case. The findings of the proposed optimized system demonstrate that under key real vehicle operating events, PMS vibration performance is enhanced by the better decoupling of the rigid body modes (RBM) parameters. This study's main contribution is the observation that by treating PMS and MDMS as a coupled system during PMS design, vehicle vibration behavior can be further improved. The approach of considering and formulating real vehicle events helps to reduce the gap between the theoretically predicted and practical measured vibration performance of PMS.