Orphans and vulnerable children affected by HIV/AIDS (HIV OVC) are at risk for cognitive difficulties and lack of access to education. Interventions addressing cognitive or educational outcomes for HIV OVC worldwide were examined through systematic searches conducted from October 2016 to 2019. We examined the summative effectiveness of interventions and the specific effects of participant age and intervention length. Interventions targeting cognitive outcomes had a small, significant effect, with no effect of moderating variables. Interventions targeting educational outcomes had significant effects. Educational interventions over 1 year were effective, but effects of intervention length were not significant. Overall, this review provides support for the effectiveness of interventions targeting cognitive and educational outcomes for OVC and highlights the need for more research on such interventions.