The recent COVID-19 pandemic reveals the vulnerability of global supply chains: the unforeseen supply crunches and unpredictable variability in customer demands lead to catastrophic disruption to production planning and management, causing wild swings in productivity for most manufacturing systems. Therefore, a smart and resilient manufacturing system (S&RMS) is promised to withstand such unexpected perturbations and adjust promptly to mitigate their impacts on the system’s stability. However, modeling the system’s resilience to the impacts of disruptive events has not been fully addressed. We investigate a generalized polynomial chaos (gPC) expansion-based discrete-event dynamic system (DEDS) model to capture uncertainties and irregularly disruptive events for manufacturing systems. The analytic approach allows a real-time optimization for production planning to mitigate the impacts of intermittent disruptive events (e.g., supply shortages) and enhance the system’s resilience. The case study on a hybrid bearing manufacturing workshop suggests that the proposed approach allows a timely intervention in production planning to significantly reduce the downtime (around one-fifth of the downtime compared to the one without controls) while guaranteeing maximum productivity under the system perturbations and uncertainties.