Regional economic development research must engage with empirical questions and policy evaluations and America's underlying anti-urban bias, which shapes American cities and policy. Standard mathematical microeconomic-founded models are a limited guide to analysis and interpretation; empirical work should consider other disciplines in addition to diverse economic perspectives. Underlying structural factors may be difficult to analyze but need attention, including federal and state hostility to cities, fragmented metropolitan forms that maldistribute urban economic output, and structural racism's impact on economies, housing, and labor markets. Doing strong empirical work while de-emphasizing theory building seems the best way to proceed.