The primary concerns of the automotive industry are structural integrity and battery-pack system (BPS) reliability. To ascertain the appropriate thickness of critical BPS components (e.g., the long bracket, crossbeam, and bottom shell), engineers are required to perform several simulations of finite element (FE) analysis. This procedure is laborious and requires a significant amount of time. This study introduces a very effective approach for predicting vibration-induced stress and fatigue life, intending to enhance dependability in the design process. Firstly, a three-layer lithium battery model is utilized to investigate the impact of vibration on the maximal Mises stress at various states of charge. This information is used to model the BPS, including the batteries. The nonlinear FE model of the BPS is validated using the modal test results. Secondly, a sensitivity analysis is performed to ascertain the impact of component thickness on the maximum Mises stress. For vibration simulations, multiple design variables are selected to collect data. Next, the nonlinear relationship between inputs (thicknesses of critical components) and outputs (maximum Mises stress and minimum fatigue life) is described using a deep learning (DL) modeling framework with forward and backward propagation. Finally, the accuracy of the DL model is assessed by measuring error functions and comparing its performance to six commonly employed methods. Furthermore, the inclusion of Gaussian noise is employed to assess the model’s robustness and ability to generalize. Additionally, the establishment of fatigue-life and stress boundaries serves to offer designers valuable insights. The results indicate that the proposed method for predicting vibration stress and fatigue life is highly efficient and cost-effective, making it useful for the design of a robust and reliable BPS.