In arid and semiarid regions, the plants suffered from water and nutrient deficiency, therefor the need for proper management of both irrigation water and nutrient especially nitrogen was obligate. The current study aimed recognize the most proper rate of nitrogen fertilizer in conjunction with water regime that achieve the best production of sesame crop grown on poor fertile sand soil. In this regard, a field experiment was carried out on sesame plants during 2020 summer season following the split-plot design, where the main plots comprised irrigation water regime (W) as a percentage from ETc (70, 85 and 100%) and the sub-plots comprise nitrogen fertilization rates (N) (50.0, 60.7 and 71.4 kg N ha^-1). Results indicated that the highest seed yield, N uptake by seeds, ¹⁵N derived from fertilizer (Ndff), ¹⁵N yield derived from fertilizer (Nydff), fertilizer ¹⁵N recovery (FNR), fertilizer ¹⁵N remaining in the soil (N_rem) and N loss were given by treatments receiving the moderate levels of both water and N fertilizer. Moreover, the combined treatment of high water regime and low N rate enhanced the nitrogen use efficiency (NUE), while the highest water use efficiency (WUE) was detected under conditions of low irrigation regime and moderate N rate. Therefore, application of 357.4 m³ ha^-1 irrigation level and 60.7 kg N ha^-1 rate was recognized as the most proper management practice achieved the efficient water-nitrogen combination that minimized N loss by any mechanism.