Diarrheal disease burden has become more heterogenous in low- and lower middle-income countries as access to clean water, sanitation and health care has increased in wealthier urban populations. Enterotoxigenic Escherichia coli (ETEC) and Shigella are among the top five causes of diarrheal mortality in children living in sub-Saharan Africa. Here, we explored how accounting for subnational and economicheterogeneity in ETEC and Shigella disease burden affects projected vaccine impact and cost-effectiveness of standalone ETEC and Shigella vaccines during the first decade after introduction in four sub-Saharan African countries. We developed dynamic models for provincial areas and socioeconomic subpopulations of children in the Democratic Republic of Congo (DRC), Kenya, Zambia, and Zimbabwe. We estimated deaths and morbidity due to ETEC and Shigella diarrhea plus additional deaths from other infectious diseases attributable to ETEC- and Shigella-induced stunting. We analyzed cost-effectiveness using Incremental Cost-Effectiveness Ratios (ICERs) with Disability-Adjusted Life Years (DALYs) and Moderate-and-Severe Diarrheal episodes (MSD) averted as denominators.