This report focuses on the case study of the Boston area and allows identifying key success factors in the Boston regional innovation ecosystem. It discusses how the macro-innovation eco-ecosystem is composed by a variety of interconnected micro-innovation eco-systems, mutually reinforcing each other and making the entire “territorial” system successful. The spatial configuration of these micro-innovation ecosystems at the urban scale has been specifically investigated, thus leading to theorize that the Innovation District may act as enabler for place-based innovation. Evidence from the Boston case study shows that there is not a single magic recipe for the successful implementation of place-based and social innovation-driven strategies. On the contrary, the variety of place-grounded combinations of micro and macro initiatives, embedded in the social and spatial fine grain of places and encompassing a diversity of actors, can create the conditions enabling places to thrive and local economic activities to grow in a sustainable way.