Tomato (Lycopersicon esculentum (L.) Mill) of the family Solanaceae, is one of the most important vegetable crops in Ethiopia. Even though, production and productivity of the crop is far below the world average, which is mostly associated with lack of improved varieties and inappropriate fertilizer application rate. An experiment was conducted to evaluate the response of application of different set of fertilizers on tomato varieties in the growing season of 2019/2020. The treatments were consisted of five levels of set of fertilizers (NPs, 0 Urea 0 and KCl 0) kg ha-1 ,,( NPs ,525 Urea, 525 and KCl, 875)kg ha-1, ( NPs ,656 Urea 656 and KCl,1094)kg ha-1,( NPs,394 Urea ,394 and KCl 656)kg ha-1,( NPs,242 Urea 79 and KCl,0)) kg ha-1 and three tomato varieties (Shanty PM, Galilea and Roma VF). The experiment laid out in 3x5 randomized complete block design in factorial arrangement with four replications. Growth and yield parameters of the tomato collected and analyzed using SAS version 9.2. Results revealed that application of set of fertilizers and tomato varieties had very highly significantly (P<0.001) influenced plant height, numbers of different levels of branches, days to 50% flowering, days to 50% maturity, number of clusters per plant, number of fruits per cluster, marketable yield, total yield. The combined effect of cultivar (Shanti PM) and application of highest set of fertilizers (NPs (656), Urea (656) and KCl (1094)) kg ha-1 delayed 50% maturity by 93 days and the highest plant height recorded (88.5cm). Generally, the combination of Shanti variety and the highest set of fertilizer application increased the growth parameters of tomato including plant height, number of branches and number of clusters. The highest marketable fruit yield (116.48t ha-1) and total fruit yield (118.50) of tomato were recorded from the treatment combination of Shanti PM Variety and the highest set of fertilizer application. There were statically similar TSS and SAR of shanti PM and Roma VF but Galilea was lower compared to the two varieties. The highest net benefit (1,014,448.00 birr) was recorded on the treatment combination of Shanti PM with set of fertilizer application NPs (656 kg ha-1), Urea (656 kg ha-1) and KCl (1094kg ha-1) with marginal rate of return (529.94%) which is above the accepted level of MRR (100%). The second highest net benefit (983,860.00 birr) with marginal rate of return 16460 %, which was obtained, by the second highest fertilizer application rate with Shanty PM can be recommended for economical production of tomato in the study area and areas with similar agro-ecologies. Furthermore, as the study was conducted at one location for a single season, repetition of the study across different agro ecologies with different irrigation systems since experiment was done by drip irrigation system.