Recent years have brought a renewed focus on the importance of manufacturing to the health and future growth of nations and regions. Several studies have highlighted the need to maintain and build manufacturing capabilities to support economic growth and have linked a nation’s as well as region’s strength in manufacturing to its ability to innovate. In the U.S., where a manufacturing strategy has largely been absent for the past 25years, advanced manufacturing capabilities are now seen as essential to the development of new products and processes across a range of industries. Against this backdrop, Massachusetts presents an interesting case since manufacturing in this U.S. state is integral to several of its most important industry clusters, yet it is a high wage, high costs state that must compete globally. This research examines the pathways and opportunities for building and fostering innovation capacity among Massachusetts manufacturers, with a particular focus on small and medium-sized enterprises (SMEs). We employ a systems approach to conduct analytic and empirical analyses that consider how knowledge and sources of innovation flow between key participants within the manufacturing innovation ecosystem. We find that the Massachusetts manufacturing innovation ecosystem is rich in terms of assets but relatively poor in terms of interconnectedness between those assets. In addition, rather than being focused on demand-driven innovation and technological upgrading for SMEs, non-market state-supported manufacturing intermediaries are primarily focused on supply-side, point solutions that work with individual firms rather than at a systems level.