: Long-lasting insecticidal nets (LLINs) have significantly reduced the malaria burden in recent decades, and this malaria prevalence reduction has been achieved through the upgrading of pyrethroid long-lasting insecticidal nets. However, this reduction has stalled due to many factors, including rapidly developing pyrethroid resistance. The protocol was registered in PROSPERO, and we used Cochrane methodology to assess bias and evidence quality. Three reviewers extracted data from individual studies, and a meta-analysis was performed using Excel and STATA version 17, expressing the data as a risk ratio. : A study involving 21,916 households from 11 randomized controlled trials showed that the chlorfenapyr treatment group had a 10% reduction in malaria infection risk, with a pooled overall prevalence of 25.96 per 100 children in the chlorfenapyr group and 32.38 per 100 children in the piperonyl butoxide group, compared to 41.60 per 100 children in the control (pyrethroid-only) group. This meta-analysis determined that the entomological outcomes of effectiveness and efficacy showed that these treatments effectively reduced vector density per household per night and mean inoculation rates, with a 23% reduction in chlorfenapyr, a 7% reduction in pyrethroid-only treatments, and a 12% reduction in piperonyl-butoxide-treated groups. This study shows that chlorfenapyr (CFP) and pyriproxyfen (PPF) LLINs are highly effective and more efficacious in reducing malaria infection, case incidence, and anemia among children, as well as in reducing mean indoor vector density, mean entomological inoculation rate, and sporozoite rate, compared to pyriproxyfen (PPF) LLINs in Africa. : This study found that chlorfenapyr (CFP) LLINs are highly effective and more efficacious in reducing malaria infection, case incidence, and anemia among children in Africa. Therefore, policymakers and health planners should place strong emphasis on addressing the effectiveness, efficacy, and resistance management of LLINs as part of their current public health agenda to eliminate malaria.