Innovation Districts are rising as the banners of the new urban, economic, and social paradigm and as a solution to the renaissance of inner cities since they expedite the creation and commercialization of new ideas which leverage the city goals and its technologic and economic attributes. The configuration of accurate indicators to measure the degree of achievement of the innovation district goals is one of the main requirements to ensure district proper development. Even when the study of innovation districts is a topic that is increasingly under study, little is still known about the insight, and it is still needed tools that favor their evolution and development. The aim of this paper is two-fold: on the one hand, it seeks to collect and analyze the indicators that have been used in literature to measure the degree of maturity over the course of the 20-year existence of the 22@Barcelona, an area of innovation that transformed an old industrial district into a knowledge-based one. On the other hand, guided by the four dimensions of the Knowledge Base Urban Development theory and the main actors that make up Triple Helix approach, the paper designs a framework of indicators in the four spheres that shape the regeneration of the district, that is, urban, economic, social and governance. As we shall see, a total of 47 indicators are proposed, indicating for each of them: the environment in which it is applied, the main purpose to which it responds, and the main actor with the greatest power of action over it.