 We examined socio-economic, rural-urban, and racial differences in cancer mortality in the United States. We found that those living in more deprived areas and rural areas had higher mortality rates compared to those living in more affluent and urban areas. Additionally, we observed that deprivation was associated with higher mortality rates across all cancers, while rural-urban continuum was associated with higher mortality rates for lung, colorectal, prostate, and cervical cancers. Furthermore, socio-economic inequalities were greater among black individuals compared to white individuals, even when controlling for deprivation and rural-urban status. These findings suggest that socio-economic inequalities in cancer mortality are present in the United States and may be due to differences in smoking and other cancer risk factors, screening, and treatment. This article was authored by Gopal Kasing, Shanita D. Williams, Mohamed Syapush, and others.