The food industry is the largest sector of the US economy; food touches everything from human health to the environment, climate change, economic inequality, and the federal budget. The challenges of improving the food system in the 21st century will require systemic approaches that take full account of social, economic, ecological, and evolutionary factors. This report provides an analytical framework for assessing effects associated with the ways food is grown, processed, distributed, marketed, retailed, and consumed in the United States. The framework will enable users to consider all domains and dimensions of effects, account for system dynamics and complexities, and choose appropriate methods for analysis. The report provides example applications of the framework based on complex questions about food security, animal welfare, and preservation of the environment and its resources. It also identifies health, environmental, and socioeconomic implications of the current system as well as potential metrics and some of the data required to assess the effects. The report will be an essential resource for decision makers, researchers, and others to examine the possible impacts of alternative policies or agricultural or food processing practices.