Rubber isolators are mounted between a cooling module and a carrier to isolate the car body from vibration due to the rotation of the cooling fan. The isolators should be durable against fatigue loads originating from fan rotation and road disturbance. Thus, the design of rubber isolators is required to maximize both vibration isolation and fatigue life. In this study, the shapes of the rubber isolators are optimally designed using a process integration and design optimization (PIDO) tool that integrates the various computer-aided engineering (CAE) tools necessary for vibration and fatigue analyses, automates the analysis procedure and optimizes the design solution. In this study, we use CAE models correlated to the experimental results. A regression-based sequential approximate optimizer incorporating Process Integration, Automation and Optimization (PIAnO), a commercial PIDO tool, is employed to handle numerically noisy responses with respect to the variation in design variables. Using the analysis and design procedure established in this study, we successfully obtained the optimal shapes of the rubber isolators in two different cooling modules; these shapes clearly have better vibration isolation capability and fatigue lives than those of the baseline designs used in industry.