Since February 2020, severe economic disruption, policy responses, and behavioral shifts have created an uncertain economic future at the global, national, state, and local levels. In the context of this uncertainty, private and governmental decisions need the best available forecasts of long-term economic and demographic growth and change, and a regional economic modeling framework that allows model users to develop alternative forecasts. This commentary provides 10-year economic and population forecasts for the top 20 U.S. metropolitan areas, using REMI—a comprehensive economic/demographic forecasting model. While it focuses on metropolitan areas, the fundamental demographic and economic factors that guide the future of a region are the same. States, cities, and rural areas have underlying demographic and economic forces that will determine their destiny.