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Groundnut is a vital food and cash crop in Ghana, contributing to protein supply and livestock fodder. However, yields lag behind potential due to soil fertility limitations. Iron (Fe) and boron (B) are essential micronutrients involved in chlorophyll formation, reproductive development, and seed set in legumes, and their foliar application can influence growth and yield. This study aimed to evaluate the interactive effects of foliar Fe and B on growth performance, yield, and nutrient uptake of two groundnut genotypes grown at two Ghanaian locations, with the goal of identifying nutrient management strategies to enhance productivity under local agro-ecologies.The experiment followed a factorial arrangement (Fe × B × genotype × location) in a completely randomized design with three replications. Treatments comprised Fe at 0, 0.6, and 0.9% and B at 0, 0.3, and 0.45%, applied as foliar sprays. The two groundnut genotypes tested were Yenyawoso and Dehye, and trials were conducted at Fumesua and Akomadan research stations. Growth and yield parameters measured included plant height, number of leaves, number of branches, pods per plant, chlorophyll content (SPAD), leaf area index, biomass yield, and grain yield. Nutrient uptake was assessed to gauge micronutrient status in tissues. Data were analyzed for main effects and interactions (genotype × location × Fe × B) at P ≤ 0.05. The results showed significant effects of genotype, location, and their interaction on plant height, number of leaves, pods per plant, and grain yield, indicating that genotypic and environmental contexts modulate response to micronutrient sprays. Across genotypes and locations, the highest yields and favorable growth were generally associated with the Fe0.9% × B0.45% combination, though performance was trait- and site-dependent. Chlorophyll content, leaf area index, and total biomass were significantly influenced by Fe and B treatments. Overall, Yenyawoso tended to outperform Dehye for several traits under the combined micronutrient regimes, but the magnitude of response varied by location. Drought stress encountered during the trial period likely constrained maximal responses and may have amplified genotype- and site-specific differences. Microscale foliar applications of Fe and B can enhance growth and yield attributes of groundnut in Ghanaian agro-ecologies, with genotype and location shaping the magnitude of response. The findings support the potential of integrating Fe and B foliar nutrition into Ghana’s groundnut production systems, but further multi-location trials under different moisture regimes are recommended to confirm stability and to optimize dosage and timing.