Iron deficiency anemia (IDA) is a persistent public health challenge in India, particularly among adolescent girls. Despite the use of Iron–Folic Acid (IFA) intervention, the IDA prevalence remains high due to variability in the degree of hemoglobin (Hb) response to supplementation. This study aimed to investigate whether the baseline levels of vitamin-A and pro-inflammatory cytokines influence the Hb increase following IFA supplementation in adolescent girls with IDA. Blood samples were collected from girls aged 15–19 y at baseline (day-0) and after 3 months of supplementation (day-90). The Hb was estimated using an analyzer, serum levels of ferritin, TfR, hepcidin, IL-6, TNF-α were measured using ELISA and vitamin A was estimated using HPLC. Based on the change in Hb (day-0–day-90), the response was categorized as good (≥1.0 g/dL) and inadequate (<1.0 g/dL). Nearly 50% IDA subjects exhibited inadequate Hb increment. This group had elevated IL6 levels and decreased vitamin-A levels compared to the good Hb><1.0 g/dL). Nearly 50% IDA subjects exhibited inadequate Hb increment. This group had elevated IL6 levels and decreased vitamin-A levels compared to the good Hb response at baseline (p<0.05). Logistic regression demonstrated a significant association between lower baseline vitamin A levels and increased odds of inadequate Hb response, particularly in moderate IDA subjects (OR=1.28, p<0.05). A direct association was observed between baseline retinol and Hb, this relationship likely to be dependent on IL-6 levels. In conclusion, low vitamin A status is a significant limiting factor contributing to the inadequate Hb increment during IFA supplementation, which may be particularly relevant in regions where vitamin-A deficiency is still a public health concern.