Abstract: This paper uses the panel data of three provinces and one city in the Yangtze River Delta from 2011 to 2021 to investigate the impact of advanced manufacturing agglomeration on the optimization and upgrading of manufacturing structure, and further explores the mediating role of technological innovation. The results show that the agglomeration of advanced manufacturing industries has a direct promoting effect on the upgrading and rationalization of manufacturing structure; and technological innovation has a significant mediating effect in the process of advanced manufacturing agglomeration promoting the upgrading of manufacturing structure, but has no significant impact on the rationalization of manufacturing structure. Finally, several countermeasures and suggestions are proposed to promote the optimization and upgrading of the manufacturing structure, from the perspective of technological innovation and advanced manufacturing agglomeration.