The industrial revolution and urbanization fundamentally restructured populations’ living circumstances, often with poor impacts on health. As an example, unhealthy food establishments may concentrate in some neighborhoods and, mediated by social and commercial drivers, increase local health risks. To understand the connections between neighborhood food environments and public health, researchers often use geographic information systems (GIS) and spatial statistics to analyze place-based evidence, but such tools require careful application and interpretation. In this article, we summarize the factors shaping neighborhood health in relation to local food environments and outline the use of GIS methodologies to assess associations between the two. We provide an overview of available data sources, analytical approaches, and their strengths and weaknesses. We postulate next steps in GIS integration with forecasting, prediction, and simulation measures to frame implications for local health policies. Expected final online publication date for the Annual Review of Public Health, Volume 45 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.