In this paper, a systematic model-based calibration framework basing on robust design optimization technique is developed for engine control system. In this framework, the control system is calibrated in an optimization fashion where both performance and robustness of the closed-loop system to uncertainties are optimized. The proposed calibration process has three steps: in the first step, the optimal performance of the system at the nominal conditions, where the effects of uncertainties are ignored, is computed by formulation of the controller calibration as an optimization problem. The capabilities of the controller are fully explored at nominal conditions. In the second step, the robustness and sensitivity of a selected control design to the system uncertainties are analyzed using Monte Carlo simulation. In the third step, robust design optimization is applied to optimize both performance and robustness of the closed-loop system to the uncertainties. The robustness capabilities of the controller are fully explored and the one that satisfies both performance and robustness requirements is selected. This process is implemented for the calibration of an advanced diesel air path control system with a variable geometry turbocharger (VGT) and dual loop exhaust gas recirculation (EGR) architecture.