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A cross-disciplinary rapid scoping review was carried out, generally following the PRISMA-SCR protocol to examine historical racial and caste-based discrimination as structural determinants of health disparities in the 21st century. We selected 48 peer-reviewed full-text articles available from the University of Memphis Libraries database search, focusing on three selected case-study countries: the United States (US), Canada, and Nepal. The authors read each article, extracted highlights, and tabulated the thematic contents on structural health disparities attributed to racism or casteism. The results link historical racism/casteism to health disparities occurring in Black and African American, Native American, and other ethnic groups in the US; in Indigenous peoples and other visible minorities in Canada; and in the Dalits of Nepal, a population racialized by caste, grounded on at least four foundational theories explaining structural determinants of health disparities. The evidence from the literature indicates that genetic variations and biological differences (e.g., disease prevalence) occur within and between races/castes for various reasons (e.g., random gene mutations, geographic isolation, and endogamy). However, historical races/castes as socio-cultural constructs have no inherently exclusive basis of biological differences. Disregarding genetic discrimination based on pseudo-scientific theories, genetic testing is a valuable scientific means to achieve the better health of the populations. Epigenetic changes (e.g., weathering—the early aging of racialized women) due to the DNA methylation of genes among racialized populations are markers of intergenerational trauma due to racial/caste discrimination. Likewise, chronic stresses resulting from intergenerational racial/caste discrimination cause an "allostatic load", characterized by an imbalance of neuronal and hormonal dysfunction, leading to occurrences of chronic diseases (e.g., hypertension, diabetes, and mental health) at disproportionate rates among racialized populations. Major areas identified for reparative policy changes and interventions for eliminating the health impacts of racism/casteism include areas of issues on health disparity research, organizational structures, programs and processes, racial justice in population health, cultural trauma, equitable healthcare system, and genetic discrimination. [ABSTRACT FROM AUTHOR]