Low planting density and deficient nitrogen application are factors that significantly decrease the yield of pearl millet in Pakistan. Optimizing their management is imperative in increasing millet production efficiency, especially with N fertilization, which can strongly affect hybrid millet response. Therefore, a field experiment was conducted at the Agronomic Research Area, University of Agriculture, Faisalabad (semi-arid) and the Agronomic Research Station, Karor Lal Eason, District Layyah (arid) over two summer seasons (2015 and 2016). The experiment consisted of three intra-row spacings (10, 15, and 20 cm) as main plots, while four nitrogen rates (0, 150, 200, and 250 kg ha−1) were randomized in subplots. The treatments were triplicated each year at both locations. The results depicted a significant change in millet crop development with a change in planting density and nitrogen rate in semi-arid and arid environments. The decrease in planting density resulted 1–2 day(s) delay in 50% flowering, milking, and maturity in semi-arid and arid region during both years of study. Higher dry matter accumulation was observed at medium planting density (15 cm intra-row spacing) and higher levels of nitrogen (250 kg ha−1) at both locations and growing seasons. The yield and attributed yield performed well with 15-cm plant spacing coupled with N application from 150–200 kg ha−1, and resulted in high nitrogen use efficiency (NUE). The results of the quadratic relationship and economic analysis linked with yield and nitrogen levels at 15-cm spacing showed 176 and 181 kg N ha−1 optimum levels (mean of years) against the economic N levels of 138 and 137 kg N ha−1 for Faisalabad and Layyah, respectively. The benefit–cost ratio (BCR) showed 31% and 45% mean excessive N at 200 and 250 kg N ha−1, in Faisalabad and Layyah, respectively. So, it is concluded that the optimum economic level of N should be sought out according to the soil and climate of an area for the production of hybrid pearl millet on a sustainable basis.