Using a sample of 122 county-level units in the Yangtze River Delta (YRD) region from 2000 to 2017, this study employs a difference-in-differences model (DID) to examine the impact of regional integration strategy (RIS) on city-region formation and a difference-in-difference-in-difference model (DDD) to test whether it has spatial heterogeneity. The results indicate that RIS has a significant positive impact on industrial integration while it also displays obvious industrial heterogeneity and spatial heterogeneity. The results of the present study contribute to the following points: First, the implementation of RIS promotes a balanced layout of the secondary industry in the region, yet the tertiary industry tends to agglomerate towards central cities. Furthermore, we found that RIS has a more significant negative effect on the integration of the secondary industry and tertiary industry in cities adjacent to metropolis. Consequently, RIS magnifies the “agglomeration shadow” within city regions in terms of industrial integration. Last, our in-depth fieldwork on Jiaxing unravels the mechanism of the shadow effect of RIS.