For assessing the adaptability of cotton cultivars (CIM-496 and NIAB-111) in Cotton-Wheat cropping system of Punjab under arid climate of Multan and response of different nitrogen (N) increments (50, 100, 150 and 200 kg N ha-1) for efficient and effective resource (nitrogen) utilization. The study was conducted in Multan during cotton growing season in 2014. Cultivars as well as nitrogen increments significantly contributed to the related traits of cotton growth, seed cotton yield and yield attributes. Increasing N increments reveals a positive association with biomass accumulation (growth), yield and yield associated components. Among N increments, 200 kg ha-1 achieved more number of bolls per plant (31.00), average weight per boll (3.48 g) and ultimately lead to higher seed cotton yield (2.42 t ha-1) as compared to other N rates (50, 100, 150 kg ha-1). Significant differences were also observed in cultivars, CIM-496 produced higher seed cotton yield than other under arid climate of Multan in Cotton-Wheat Cropping system. Empirical model was developed on the basis of field observations to compute the seed cotton yield beyond the application of 200 kg N ha-1. It is predicted that seed cotton yield increased with additional increment of nitrogen (>200 kg ha-1) but it is not significant change in yield per unit increment as compared with previous ones.