Based on China’s provincial panel data from 2012 to 2022, a two-way fixed effects model, spatial Durbin model, and moderation effect model were used to empirically test the impact of innovation factor agglomeration on the high-quality development of the manufacturing industry. The results show that the agglomeration of innovation factors can promote the high-quality development of manufacturing industry, and at the same time, hinder the high-quality development of manufacturing industry in neighboring areas while promoting the high-quality development of local manufacturing industry. The positive regulatory effect of digital transformation on the agglomeration of innovative factors and the promotion of high-quality development in the manufacturing industry was significant in the eastern region, but not significant in the central and western regions. The digital transformation positively regulated the relationship between the agglomeration of innovation factors and the high-quality development of manufacturing industry in the local area, with weak regulatory effects on geographically adjacent regions and strong regulatory effects on economically adjacent regions. The agglomeration of innovative factors in high marketization areas can promote the high-quality development of the manufacturing industry more significantly, compared to low marketization areas. Finally, policy suggestions are put forward, including promoting regional innovation cooperation,strengthen the construction of digital infrastructure, and facilitate the appropriate aggregation of innovation factors.