We aimed to examine poverty and rurality as potential predictors of cancer health disparities. This cross-sectional study used data from the Florida Cancer Data System on all cancer diagnoses in the years 2014-2018 to determine age-adjusted incidence and mortality (per 100,000 population) for the 22 most common cancer sites within rural and urban counties, and high poverty and low poverty communities. Rural/urban and high/low poverty related cancer disparities were tested for statistical significance using the Rate Ratio statistical test. Overall cancer incidence was significantly lower in rural areas than in urban, but significantly higher in high poverty communities. Rurality and poverty were both associated with disparity in cancer incidence risk for tobacco-related cancers. The overall mortality was 22% higher in high poverty areas compared to low poverty areas. Ten cancer sites had mortality disparity from 83% to 17% higher in high poverty areas. Only three cancer sites, all tobacco-related, had higher mortality in rural areas than urban areas, demonstrating the intersectional nature of inhaled and smokeless tobacco use in rural low-income communities. Cancer and mortality rates in rural and urban areas may be largely driven by poverty. The high disparities related to high poverty areas reflects poor access to preventative care and treatment. Low income communities, rural or urban, will require focused efforts to address challenges specific to each population.