Enhancing the resilience of industrial chains, accelerating the empowerment of new quality productive forces, and building a modern industrial system are key to advancing regional innovation and achieving high-quality regional development. Currently, as the global industrial and supply chains undergo restructuring, external uncertainties have risen significantly. China’s industrial chains are confronted with multiple risks, such as “chain breakage, chain shortage, and chain congestion”, making it imperative to take innovation-driven development as the core to build a modern industrial system with high resilience and strong security. Anchored in innovation-driven development, new quality productive forces can provide a new driving force for the development of industrial chains and effectively enhance the resilience and security of industrial chains. To clarify the logical relationship between regional innovation ecosystems and industrial chain resilience, this paper explores their interaction mechanisms from the perspectives of policy environment, resource factors, diversified industries, digital technology, and complex culture. It constructs an evaluation index system for regional innovation ecosystems and industrial chain resilience, and conducts an empirical analysis based on panel data from 30 provincial-level regions in China from 2010 to 2023. The findings reveal that industrial chain resilience has significant inertial characteristics, and the optimization of regional innovation ecosystems contributes to the improvement of industrial chain resilience. Additionally, improvements in economic development, financial development, and government support can effectively enhance industrial chain resilience, while a higher level of opening-up may exacerbate industrial chain risks. Accordingly, it is necessary to optimize practical pathways by refining policy layouts, strengthening factor integration, enhancing industrial clusters, promoting digital transformation, and building innovation ecosystems, thereby comprehensively building regional innovation ecosystems and effectively enhancing industrial chain resilience.