Based on the data of A-share listed advanced manufacturing companies in Shanghai and Shenzhen from 2014 to 2023, this study explores the impact effects and mechanism of the establishment of national manufacturing innovation centers on the breakthrough of key core technologies. The research findings are as follows: the implementation of national manufacturing innovation centers has significantly promoted the key core technological innovation of advanced manufacturing enterprises. This conclusion remains valid under various robustness tests. The mediating effect indicates that the efficiency of innovation factor allocation, innovation chain collaboration, and computing infrastructure construction serve as important mediating role in the process where national manufacturing innovation centers influence the breakthrough of key core technologies of advanced manufacturing enterprises. Heterogeneity analysis reveals that the policy effect shows significant differentiation in terms of enterprise type and urban level. The manufacturing innovation centers exhibit stronger innovation impact effects in non-state-owned enterprises, enterprises with higher innovation emphasis, and first-tier and new first-tier cities.