Tomato yield can be increased by the application of optimum water and fertilizer. A field experiment was conducted in Efratana Gidim district, North Shewa, Amhara, Ethiopia, during 2019 and 2020. The objective was to determine the nitrogen (N) rate and irrigation regime for optimum tomato yield and water use efficiency (WUE). The experiment consisted of three-irrigation regimes (75% ETc (Evapotranspiration from the crop), 100% ETc, and 125% ETc) and four nitrogen (N) rates (control; i.e. without N application1, 46 kg N ha−1, 92 kg N ha−1, and 138 kg N ha−1). The treatments were laid out in a split-plot design with four replications. The Irrigation regime were assigned to the main plot, while the N rate were assigned to the subplot. Data on growth, yield, and yield-related traits of tomatoes, include; plant height, number of fruit clusters per plant, fruit length, fruit diameter, number of marketable fruits, number of un-marketable fruits, the total number of fruits, marketable fruit yield, un-marketable fruit yield, total yield were collected. The data were subjected to analysis of variance using R studio. The results indicated that the experimental site had low total N content, and the application of N fertilizer significantly improved tomato yield. Increasing irrigation depth also significantly increased tomato yield. The result indicated that the highest mean marketable fruit yield (35,903 kg ha−1) was obtained from the combined application of 125% ETc with 92 kg N ha−1, while the lowest (13,655 kg ha−1) marketable fruit yield was obtained from 75% ETc with 92 kg N ha−1. The analysis of variance showed that the highest (5.4 kg m−3) WUE recorded from 75% ETc with 46 kg N ha−1 increased WUE by 77% (2.4 kg m−3) compared with the lowest (2.3 kg m−3) WUE recorded from 125% ETc with 0 kg N ha−1. The partial budget analysis also indicated that the highest net benefit (266,272 ETB (Ethiopian Birr) ha−1) and an acceptable marginal rate of return (1240%) for the invested capital was recorded from the combined application of 125% ETc with 92 kg N ha−1. Therefore, the application of 125% ETc with 92 kg N ha−1 resulted in the highest net benefit.