INTRODUCTION: Multiple micronutrient deficiencies might increase the adverse outcome during pregnancy and after birth. Considering the WHO recommendations since 2016 and scientific evidence from previous studies that multiple-micronutrient supplementation (MMS) is more effective than iron folic acid (IFA) in improving pregnant women's health, it is imperative to conduct an economic evaluation to assess the cost-effectiveness of MMS compared with IFA. METHODS: We conducted a systematic review from PubMed and Scopus to identify the cost-effectiveness analyses of MMS compared to IFA for pregnant women up to January 2024. Data extraction included specific study characteristics, input parameters, cost elements, cost-effectiveness results, and key drivers of uncertainty. This systematic review adhered to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: After removing 111 duplicates and following the screening process on the title and abstract of 1201 records, resulting in 125 full-text articles assessed for eligibility, a total of 5 studies fulfilled the inclusion criteria and were included in the review. All included studies were from low- and middle-income countries and demonstrated that MMS compared to IFA for pregnant women is cost-effective and even very cost-effective in some countries. All included studies implemented cost-effectiveness analysis (CEA) and estimated its cost-effectiveness using incremental cost-effectiveness ratio (ICER) per disability-adjusted life years (DALY) averted. Results suggested that the transition from IFA to MMS was cost-effective. The range of ICER per DALY averted in this study is USD 3.62 to USD 1024, depending on the scenario. Overall, the main determinant influencing cost-effectiveness was the cost of MMS procurement. CONCLUSION: Our findings highlight that transitioning from IFA to MMS in certain conditions has been proven cost-effective, emphasizing this intervention's economic viability. MMS price and micronutrient deficiency-related disease burden are important determinants in assessing cost-effectiveness. REGISTRATION: PROSPERO CRD42022319470.