<p>Heavy metal-mediated environmental pollution is of global public health importance. This is due to the growing anthropogenic activities hence the present study that evaluated heavy metals uptake in <i>Cricetomys gambianus</i> (<i>C. gambianus</i>) within the Federal Capital Territory, Nigeria, vis-à-vis its direct histopathological effects in the rats themselves and indirectly, health risks to their human consumers (children, adolescents, adults, and geriatrics). Heavy metals, health risk and histopathological assessments/evaluations were performed according to standard procedures and protocols. Only the concentrations of cadmium (Cd), lead (Pb), chromium (Cr), and arsenic (As) were above and beyond their recommended permissible limits to pose health risk to their human consumers. The lifelong intake of the present concentrations of Cd, Pb and Cr individually and all the heavy metals cumulatively posed major health risk to the human consumers based on the health risk assessment protocols. Arsenic was the most hazardous heavy metal with the highest relative risk value in the present study compared to others. There were evidences of degenerative, necrotic and inflammatory changes in the lungs, liver, testes, and epididymis of the sampled rats. However, no significant differences existed in the degree of tissue change between the evaluated organs. The results revealed high concentrations of heavy metals in <i>C. gambianus</i> within the study area with heightened human health concerns, including to the rats themselves. This requires urgent and targeted mitigative attention to safeguard and conserve both human and animal life within the study area, especially of the highly hunted and or baited <i>C. gambianus</i>.&#xa0;</p>