Understanding the framework of regional urban economic organization and its spatial effect requires a consideration of the networks. Urban network research has increasingly focused on urban spatial interaction and economic spillover effect based on the network externality theory in the context of transition from network research on structural description to performance evaluation. This study focused on Guangdong Province as the research area, built intercity passenger and freight flow networks based on the traffic, people, and express flow, studied the spatial structure of the network using social network analysis and other quantitative methods, and used a spatial Durbin model to estimate the economic spillover effect of the network. The conclusions from the results obtained can be summarized as follows. (1) In the network of traffic and people flow, Guangzhou and Foshan occupy the central positions. The core node of the express flow network spans Guangzhou, Dongguan, and Shenzhen. The spatial distribution of core linkages in the people flow network could be summarized as "the double-channel mode" of Guangzhou-Foshan and Shenzhen-Dongguan, while the corridor distribution of Foshan-Guangzhou-Dongguan-Shenzhen is the dominant flow organization pattern in the traffic flow network. In the express flow network, the dominant flow is dispersed eastward along the coast. (2) Guangzhou serves as the primary controlling entity of the network. Urban nodes clearly differ functionally in the express flow network; however, there is little functional difference in the traffic and people flow networks. (3) According to the spatial regression coefficients based on the SDM of the traffic, people, and the express flow networks, which are -0.974, -1.255, and -8.173, respectively, the economic externality of intercity passenger and freight flow networks reveal a substantial negative spillover. The current growth trend of Guangdong Province is not coordinated or complementary. (4) Coordinated expansion of the regional economy has been facilitated by improved functional connections between urban nodes. In addition, The movement of intercity factors could lower consumer market transaction costs and entrance barriers while allowing regional cities to enjoy the development advantages of borrowed size. However, the improvement of the conditions supporting the business infrastructure has expedited resource siphoning and intensified the province space's agglomeration shadow. This study created urban networks based on the movements of the passenger and freight flows, thereby enriching the empirical investigation of the externality theory in South China. This study also provides some guidance for advancing the regional economic integration and high-quality development.