The urban network is an important method of spatial optimization, and measuring the development level of the urban network is a prerequisite for spatial optimization. Combining geographic information system (GIS) spatial analysis, social network analysis, and multidimensional scaling models, we explored the evolution of the urban network spatial structure in the Yangtze River Delta from 1990 to 2017 and proposed corresponding optimization measures. The results showed that the urban network spatial structure of the Yangtze River Delta has evolved from a single-center cluster with Shanghai as its core to a multi-center network with Shanghai as its core and Nanjing, Hangzhou, and Hefei as secondary cores. The density of the urban network has gradually expanded, but the strength of the connection between edge cities such as Chizhou, Suqian, and Quzhou and the core cities needs to be further improved. We found that the evolution of the urban network spatial structure has been driven by preferential attachment, path dependence, and differences in economic and industrial development. Finally, we propose optimizing the urban network spatial structure by strengthening the driving ability of the core cities, clarifying urban functions and development directions, and establishing a unified coordination mechanism. This paper enriches and deepens our understanding of the characteristics of the city network in the Yangtze River Delta, and provides a reference for the optimization of the urban network spatial structure.