With the transition in the regional development discourse to knowledge- and innovation-based economics, the cultivation of innovation capacity has gained importance as an initiative to enhance regional sustainability and has emerged as a policy goal. An understanding of the formation of innovation clusters is critical to the cultivation of regional innovation capabilities. Except for the location and regional development conditions’ factors, researchers emphasize a built environment’s role in the formation of innovation clusters. Based on the spatial database of 12,516 high-tech firms in 2017 in the Pearl River Delta (PRD), this study developed a conceptual framework for the built environment. The framework comprises living, service, perceptual, industrial, and physical aspects. The direction and intensity of the correlation between built environment factors and high-tech firms are discussed using the spatial regression model and geographical detector (GD) technique. The results show a highly concentrated spatial distribution pattern of high-tech firms in the PRD. A significant county-level spatial autocorrelation is revealed through Moran’s I. According to the model, we determine the positive impacts of technology support, transport infrastructure, and living service levels on the agglomeration of high-tech firms as well as the negative impact of the public service level. The GD’s result demonstrates different levels of impact intensity of built environmental factors. We argue that a comprehensive understanding of the influence of built environment factors on innovation agglomeration will help policymakers develop targeted policies to foster local innovation capabilities and promote sustainable regional development.