Introduction Malaria remains a significant global health burden, especially in endemic regions where efficient use of limited resources is critical. Economic evaluations provide essential evidence to guide strategic resource allocation and optimise intervention outcomes. This systematic review synthesises recent evidence (2018–2025) on the cost-effectiveness of malaria prevention and treatment interventions in endemic settings. Materials and methods A systematic search of Scopus, Web of Science, and PubMed identified English-language studies published between 2018 and 2025. Eligible studies included full economic evaluations cost effectiveness (CEA), cost utility (CUA), and cost benefit analysis (CBA) assessing malaria prevention or treatment programs. Data extracted included intervention types, comparators, outcomes, costs, and incremental cost-effectiveness ratios (ICERs). Results Eighteen studies met the inclusion criteria, mainly randomised trials evaluating insecticide-treated or long-lasting insecticidal nets (ITNs/LLINs), indoor residual spraying (IRS), diagnostics, treatment strategies, and combined interventions. Most were conducted in Sub-Saharan Africa LLINs and IRS were highly cost-effective, with costs per disability-adjusted life year (DALY) averted below national GDP thresholds. Combined approaches enhanced effectiveness in high-resistance or high-burden settings, while complex strategies, such as tafenoquine with G6PD screening, showed higher ICERs due to additional costs and operational challenges. Conclusion Most malaria interventions in Sub-Saharan Africa were highly cost-effective, including LLINs (with PBO nets), IRS (Actellic/3GIRS), combined LLIN + IRS, SMC/PDMC, IPTp, and ACT + RDT. RTS,S vaccination and RDT + microscopy were moderately cost-effective, while G6PD screening with tafenoquine and traveller chemoprophylaxis were context-specific or less cost-effective. A socio-ecological framework underscores the need to align policies with economic evidence for optimal resource allocation and accelerated malaria elimination. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD42024546911 , PROSPERO Registration: CRD42024546911.
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