Globally, excess soil nutrient mining is a serious challenge to sustainable agricultural production. The task is more daunting in the semi-arid region of the globe. In addition to the primary nutrient deficiency over the mining of secondary nutrients, especially sulfur is an emerging challenge in contemporary crop production systems. Hence, there is a dire need to devise an appropriate sulfur management protocol by searching for efficient and sustainable sulfur sources. Therefore, the efficacy of new sulfur molecules was evaluated on the performance and nutrient acquisition potential of the pearl millet–mustard system at the research farm of the Indian Agricultural Research Institute in New Delhi, India, for two years. The flexibility of urea–ES technology allows customized sulfur-enhanced urea formulations that suit unique crop needs, offering an all-in-one nitrogen and sulfur fertilizer solution. Hence, the study hypothesized that new sulfur molecules like sulfonated urea (SEU) will have a positive impact on crop growth, yield, and nutrient acquisition in the pearl millet–mustard system. The results revealed that the application of 50% sulfur (S) (15 kg/ha) as a base and 50% (15 kg/ha) as a topdressing (SEU 10-0-0-75) produced better growth, yield-contributing parameters, and economic productivity of the pearl millet–mustard system. However, both compositions of SEU (40-0-0-13 and 10-0-0-75) were significantly better than the recommended dose of fertilizer (RDF) and the RDF along with other S sources like single super phosphate and bentonite in enhancing crop growth and productivity. The agronomic efficiency of nitrogen (AEn) and S (Aes) of SEU (40-0-0-13 and 10-0-0-75) were 9.1 and 10.3 kg seed yield/kg N and 51.2 and 28.9 kg seed/kg, respectively. The agronomic nitrogen use efficiency of SEU (40-0-0-13) and SEU (10-0-0-75) is significantly higher than those of nitrogen, phosphorus, and potassium (NPK) alone. Thus, the findings inferred that splitting S (50% as a base and 50% as topdressing) through SEU is a practically feasible and economically robust S option for profitable and sustainable production of the pearl millet–mustard production model in the semi-arid region.