Poverty is a carcinogen and a leading cause of cancer disparities and overall mortality in the United States. Poverty is often viewed as an individual failure for "being poor," but in fact, poverty is structurally driven, intergenerational, and place-based that socially deprives and denies human potential. Disparities in timely cancer prevention, diagnosis, treatment, survivorship, and survival disproportionally impact people living in poverty and especially in persistent poverty areas, an extreme form of place-based poverty that affects communities over multiple generations. There has been some progress made to address place-based conditions that exacerbate poverty, such as the NCI's initiative on persistent poverty. However, gross inequality and cancer disparities continue to exist and persist. The time is now to accelerate the development of research-informed strategies and solutions with communities along with multisectoral collaborations with education, housing, occupation/workforce, foster care, criminal justice, transportation, and data collection systems. This commentary discusses the structural, place-based, and generational context of poverty, illustrates how entrenched inequities shape poor cancer outcomes, and describes opportunities for future research.