Building an effective resilient supply chain system (RSCS) is critical and necessary to reduce the risk of supply chain disruptions in unexpected scenarios such as COVID-19 pandemic and trade wars. To overcome the impact of insufficient raw material supply on the supply chain in mass disruption scenarios, this study proposes a novel RSCS considering product design changes (PDC). An RSCS domain model is first developed from the perspective of PDC based on a general conceptual framework, i.e., function-context-behavior-principle-state-structure (FCBPSS), which can portray complex systems under unpredictable situations. Specifically, the interaction among the structure, state and behavior of the infrastructure system and substance system is captured, and then a quantitative analysis of the change impact process is presented to evaluate the resilience of both the product and supply chain. Next, a case study is conducted to demonstrate the PDC strategy and to validate the feasibility and effectiveness of the RSCS domain model. The results show that the restructured RSCS based on the proposed strategy and model can remedy the huge losses caused by the unavailability of raw materials.