Structural racism has been identified as a fundamental cause of health disparities. For example, racial, ethnic, and economic neighborhood segregation; concentrated poverty; community disinvestment; and sociocultural context influence obesity and cancer disparities. Effects of structural racism are also evident through neighborhood obesogenic conditions such as limited access to affordable and healthy foods and physical activity opportunities within segregated communities that contribute to obesity and obesity-related cancer disparities. This article describes and expands on cross-cutting themes raised during a webinar held by the National Cancer Institute (NCI): (1) how structural factors, including neighborhood segregation and obesogenic conditions within racial and ethnic disadvantaged communities, influence disparities in the United States; (2) current research challenges and best ways to address them; and (3) selected priorities of the NCI aimed at addressing multilevel and intersecting factors that influence obesity-related cancer disparities. Further research is needed to understand how residential segregation and neighborhood obesogenic conditions influence cancer prevention and control across the continuum. Identifying the best approaches to address obesity and cancer disparities using social determinants of health framework and community-engaged approaches guided by a structural racism lens will allow researchers to move beyond individual-level approaches.