Nigeria experiences high under-five mortality, partly attributed to low healthcare affordability from high out-of-pocket health expenditures (OOPHE). This study analyzed the impact of OOPHE on under-five mortality (U5M) in Nigeria from 20002021 using Poisson regression. The results showed OOPHE had an insignificant negative association with U5M. However, institutional quality, female literacy, immunization coverage, and sanitation access demonstrated significant negative relationships with U5M. The model had no overdispersion. Overall, the findings indicate institutional, socioeconomic, and health system factors like governance, education, vaccination, and water/sanitation are salient determinants of U5M outcomes in Nigeria, more so than OOPHE. While reducing OOPHE remains important for universal health coverage, the results suggest targeting improvements in government effectiveness, female literacy, immunization coverage, and sanitation access could significantly lower under-five mortality. The study contributes countryspecific evidence on drivers of child survival in Nigeria.