Entrepreneurial ecosystems (EE) and national systems of innovation (NSI) are central to the study of entrepreneurship and innovation from the geographical angle. Recent bibliometric analyses show that the number of NSI citations has boomed since 2000 (Jurowetzki et al., 2015) whereas that of the EE has increased since 2010 (Alvedalen & Boschma, 2017). Although both the EE and NSI can be considered as closely related concepts, so far, the attempts to bridge the two are scarce (Acs, Stam, Audretsch & O’Connor, 2017). The task of bridging the EE and NIS concepts involves recognizing their main commonalities and differences (Alvedalen & Boschma 2017; Stam and Spigel 2017) but also a discussion of their antecedents and evolution as well as the existing contextual differences between the Global North and the Global South. The main objective of this chapter is to build a bridge between the EE and NSI within the context of the Latin American Countries (LAC). To achieve this, we review the main contributions to both fields from the scholars based in this region and make first steps towards a common research agenda considering the LAC realities. We address the following research questions: What are the origins, paths and main commonalities and differences between the EE and the NSI? What are the central contributions made by Latin American scholars to both fields? What are the most important issues in the research agenda that bridges the EE and the NSI perspectives in the Global South?