PURPOSE Economic and social-behavioral changes over the last two decades in Latin America and the Caribbean (LAC) are associated with increases in the regional cancer burden. We aim to describe the National Cancer Institute�funded extramural research portfolio with collaborators in the LAC between fiscal years 2014 and 2018 and compare project numbers by site with subregional cancer burden. METHODS This analysis included National Cancer Institute�funded extramural projects with LAC collaborators from fiscal years 2014 to 2018 from the National Institutes of Health IMPAC II database. Projects were stratified by Pan American Health Organization�s Latin American subregions, tumor sites, and regional site-specific rates of cancer incidence and mortality using Globocan 2018 estimates. To better understand subregional variations in cancer incidence and mortality, this analysis focused on the top 5 sites of incidence and mortality in LAC after breast and prostate cancer. RESULTS Between fiscal years 2014 and 2018, 108 projects with LAC collaborators were funded. Project collaborators came from 22 countries in the region, and projects covered 20 tumor sites. The Southern Cone had the most projects funded, followed by the Central American Isthmus and Mexico, Andes, Latin Caribbean, and non-Latin Caribbean�this was roughly proportional to subregional populations. Variation exists at the subregional level for the top 5 cancers when comparing incidence and mortality with subregional project counts. Disparities between projects and incidence by tumor site were the largest for colorectal, lung, and uterine cancers. Disparities between projects and mortality by tumor site were the largest for lung and uterine cancers. Disparities between projects and both components of cancer burden by subregion were the largest for the Latin Caribbean and non-Latin Caribbean. The number of funded projects for Kaposi sarcoma and non-Hodgkin lymphoma largely outpaced both incidence and mortality in every subregion. CONCLUSION This analysis suggests that projects� alignment with cancer burden is variable by subregion, provides an understanding of cancer research funding by site, and highlights areas of interest for additional investigation, training, and collaboration in LAC.