Nitrogen (N) management remains a critical agronomic challenge due to various losses such as leaching and volatilisation which necessitate more efficient delivery mechanisms especially in acidic soils. This study investigated the N substitution potential of nano-urea in maize (Zea mays L.) cultivated under acidic soil conditions. A field experiment was conducted using a randomised complete block design with 12 treatments which compared varying levels 0 %, 50 %, 75 % and 100 % of the recommended dose of nitrogen (RDN) applied either alone or in combination with foliar sprays of nano-urea or 2 % conventional prilled urea solution. Growth kinetics revealed that the combined application of 100 % RDN with nano-urea consistently maximised crop growth rate, net assimilation rate and leaf area duration. Importantly, reducing the basal N dose to 75 % RDN while supplementing with foliar nano-urea produced physiological responses and grain yield (5.79 t ha-1) which was statistically comparable to the 100 % RDN (6.24 t ha-1). This demonstrates a 25 % RDN substitution without incurring agronomic penalties. Furthermore, this 25 % N substitution approach optimised nitrogen use efficiency (NUE); the agronomic efficiency (AE) and apparent recovery efficiency (RE) of the 75 % RDN plus nano-urea treatment remained statistically comparable to the 100 % RDN. Pearson’s correlation analysis confirms that the enhancement of growth kinetics through nano-urea directly translated into improved sink capacity and final grain yield. In contrast, conventional 2 % prilled urea sprays showed high variability and failed to provide statistically at par results. Economic analysis indicated that the 75 % RDN plus nano-urea strategy maintained net returns and a benefit-cost (B:C) ratio statistically at par to the 100 % RDN. These findings suggest that integrating foliar nano-urea with reduced N applications represents an efficient and sustainable nutrient management strategy for maize in acidic soils, reducing the economic burden and environmental footprint of excessive soil N applications while sustaining overall profitability.