To facilitate national decision-making, a cost-effectiveness model to compare supplementation approaches was developed and applied to Pakistan, India, and Bangladesh in this study. Results showed that the effectiveness of transitioning from iron folic acid (IFA) to multiple micronutrient supplementation (MMS) under the Cochrane scenario was smaller and less certain compared with The Lancet scenario. However, even under the Cochrane scenario, MMS would avert 4,391, 5,769, and 8,578 more DALYs than IFA per 100,000 pregnancies in Pakistan, India, and Bangladesh, respectively (62.6%, 76.8%, and 82.6% certainty). The incremental cost-effectiveness ratio (ICER) of transitioning from IFA to MMS was 41.54, 31.62, and 21.26 US dollars (USD 2016) per DALY averted, respectively. The study concluded that in spite of the discrepancies in the overall effect of MMS depending on the meta-analysis used, MMS is cost-effective and generates positive health outcomes for both infants and pregnant women. Further, the study recommends that whilst the effectiveness of MMS is sensitive to the prevalence of certain health outcomes under the conservative scenario (Cochrane), MMS nevertheless averts more DALYs than IFA with high certainty and should re-enter public health discussion in Pakistan, India, and Bangladesh.