Inadequate nutrient management is one of the major challenges for sustainable soybean production in semi-arid climatic conditions. Hence, a 3-year (2015–2017) field experiment was conducted to assess the effect of foliar application of macro- and micronutrients on the growth, productivity, and profitability of soybean. Eight foliar nutrient sprays at the pod initiation stage—water spray (WS), 2% urea solution, 2% di-ammonium phosphate solution (DAP2%), 0.5% muriate of potash solution (MOP0.5%), 2% solution of 19:19:19 nitrogen phosphorus and potassium (NPK2%), and a 0.5% solution each of molybdenum (Mo0.5%), boron (B0.5%), chelated-zinc (Zn 0.5%) and no-foliar nutrition (NFN)—were compared with a basal-applied recommended dose of fertilizers (RDF: 30 kg N, 75 kg P, and 40 kg K ha−1) in a randomized block design (RBD), replicated three times. Foliar-applied chelated Zn@0.5% (Zn0.5%) at the pod initiation stage resulted in more pods per plants. In addition to Zn0.5%, urea2%, NPK2%, and B0.5% significantly improved the pods per plant over treatment by no-foliar nutrition (NFN). The RDF-supplied soybean subsequently sprayed with Zn0.5% produced the highest seed yield, which was 18.5–37.8% higher than that of NFN treatment Yield improvement due to the application of B0.5%, DAP2%, and urea2% varied between 19.2–23.7, 16.6–20.4 and 18.6–20%, respectively. Foliar nutrition showed the largest net returns from Zn0.5%. The water-use efficiency (WUE) and production efficiency increased by 18.4–37.6 and 34.9–37.5%, respectively, due to Zn0.5% over the efficiencies from NFN treatment. Monetary efficiency (ME) gains due to Zn0.5% were 24% higher, while ME efficiency gains due to urea2%, NPK2%, and B0.5% varied between 15–16%. Thus, this study suggested that the foliar application of 0.5% Zn and B, urea, NPK fertilizer, and DAP at 2%, along with RDF. is a profitable nutrient management option for quality soybean production in a semiarid region. However, nutrient partitioning, changes in soil chemical and biological indicators, and environmental aspects need critical examination in future studies.