Innovative data sources offer new ways of studying spatial and temporal industrial and regional development. Our approach is to study the development of an entrepreneurial regional economy through a comprehensive analysis of its constituent firms and institutions over time. Our study region is defined by the location of large multinationals recruited to North Carolina’s Research Triangle Park and the adjacent area. We have built a database of 4200 technology-intensive entrepreneurial firms that draws on over 30 distinct data sources and includes details on company founders, annual firm employment and engagement with the entrepreneurial ecosystem. By outlining our approach in this paper, our primary objective is to create a transferable framework for analyzing regional dynamics in other locations.