Entrepreneurial ecosystem (EE) leadership is the orchestration of community resources to influence ecosystem effectiveness. In high-functioning EEs, ecosystem leaders from different organizations and sectors work together to attract and manage community resources to support entrepreneurial activity. The leaders in EEs represent a multi-team system—a team of teams that works independently and interdependently to achieve high performance for their organizations and the EE. In operating in inter-organizational teams, EE leaders must balance the pursuit of their respective organizational interests with the pursuit of collective, ecosystem goals. However, creating effective EE multi-team systems that are not fragmented by dysfunctional group dynamics is challenging. In this chapter, we leverage a stream of research focused on teams operating in extreme contexts to understand the unique challenges facing EE multi-team systems. Specifically, we draw insights from studies of teams responding to natural disasters, medical emergencies, environmental crises, and other extreme situations to understand the challenges EE multi-team systems face in developing the “3Cs”: cooperation, coordination, and communication. To address these ecosystem leadership challenges, we adapt three interventions to fit the distinctive issues faced by EE leadership: improving EE leadership through team-building experiences, enhancing the sociotechnical networks of EE leadership teams, and establishing informal policies and procedural guidelines to improve EE multi-team system functioning. We offer insights that can be used by scholars to understand the group dynamics involved in EE leadership and by ecosystem practitioners to improve the effectiveness of EEs.