Entrepreneurship is a critical driver of economic health, industrial rejuvenation, social change, and technological progress. In an attempt to determine how to best support such an important component of society, researchers and practitioners alike continue to ask why some countries, regions, and cities have more entrepreneurship than others. Unfortunately, the answer is not clear. This question is addressed by focusing on location-based support or infrastructure for entrepreneurship. A framework based on a social systems perspective guides this examination by concentrating on three main categories of infrastructure: resource endowments, institutional arrangements, and proprietary functions. Work from the knowledge-based perspective of entrepreneurship, systems of innovation, entrepreneurial ecosystems, and resource dependence literatures is integrated into this framework.