This study discusses how the role of entrepreneurship in addressing the so-called “grand challenges” (e.g., poverty, inequality, pollution, climate change) is evolving and could further evolve, based on the ongoing conversation in the scholarly community. To develop the discussion, we conducted the following steps: (1) a computer-aided semantic analysis; (2) an analysis of the evolution of literature streams; and (3) a network analysis of advocated theories and approaches. All three analyses were based on a selection of 358 publications retrieved via a keyword search and 27 further publications retrieved via an analysis of five recent and relevant special issues published by important scientific journals. Our results show that the call to address grand challenges, particularly after the publication of the United Nations’ Sustainable Development Goals (SDGs), is radically transforming entrepreneurship research, with new issues emerging and replacing traditional issues as core to the discipline, marking a rapid and complex dynamics of research stream divergence and convergence. Similarly, the network of theories and approaches advocated by recent agenda-setting articles depicts an emerging theoretical landscape that is highly innovative. This new theoretical landscape revolves around systems thinking and Ostrom’s theory of the commons as the two key poles, with the embeddedness, stakeholder, institutional, effectuation, processual, and design-oriented approaches being the cross-fertilizing forces linking these two poles. In the final section, we present the nine articles included in the special issue titled “Grand Challenges and Entrepreneurship: Emerging Issues and Research Streams” and briefly synthesize these in the light of the ongoing evolution of the literature.