Abstract: Based on the 228 cities of China as study cases, this paper summarizes six digital factors affecting urban S&T innovation under the TOE framework. Then this paper adopts the NCA method to measure the necessity degree of digital factors to promote the development of urban S&T innovation. Meanwhile the fsQCA method is selected to explore the configuration path of digital factors empowering S&T innovation from an urban scale perspective. Furthermore, 228 cities are divided into different sample sets, with the classification criteria such as the "quasi-Huanyong line", urban S&T innovation scale, and whether it is a national innovation city. After the six sample sets are calibrated and modeled separately, this paper analyzes the configuration heterogeneity of digital factors empowering urban S&T innovation. The results show that: First, there is no single necessary condition that leads to the development of high technology innovation, but industrial integration plays a universal role in promoting the development of high technology innovation in cities. Second, There are two ways to achieve high urban S&T innovation，named A1:"government support technology driven " and A2: "government promotion environment driven". Configuration A1 indicates that cities can achieve high S&T innovation improvement, with high level of information infrastructure, services digitalization, and industrial integration as the leading conditions, and solid database foundation and high government support as the supporting conditions. While A2 refers that the city can achieve high S&T innovation development when there is a complete information infrastructure, a high level of government support, services digitization, governance digitization, and industrial integration. At this time data base and digitalization of governance can be substituted with each other. Last but not least, there are clear configuration heterogeneity when cities have different geographic locations, S&T innovation scales, and innovation policies: ①governance digitalization plays a minor role in the southeast cities, while the northwest cities rely more on a high level of digital governance and industrial integration for their S&T innovation. ②government support and digital environment construction play a prominent role in technological innovation in "central cities", while "peripheral cities" depends on information infrastructure and industrial integration more.③industrial integration is critical factors for S&T innovation in national innovative cities, while non-national innovative cities still needs the linkage of information infrastructure. ④Overall, industrial integration, government support, and information infrastructure are the keys to S&T innovation improvement for all types of cities. Therefore, this paper proposes some management recommendations as follows. Firstly, all region should explore its own unique path of digitalization empowering S&T innovation, referring to the configuration template above from an overall perspective. Secondly, all cities should promote the synergy of digital service and governance of traditional government department, and form the localized digital development policy system with adaptation to local conditions, in order to provide support for cultivating a good digital environment for S&T innovation. Finally, all regions should actively promote the digital transformation of traditional industries, and build professional productive digital service platforms, promote "enterprises on the cloud" and "enterprises using the cloud", then set the digital economy industrial parks, leading to drive urban science and technology innovation with new models and new industries.