Faced with severe global shortage of water and soil resources, studies on the integrated effect of water and nitrogen on tomato cultivation are urgently needed for sustainable agriculture. Two successive greenhouse experiments with three irrigation regimes (1, 2/3, 1/3 full irrigation) and four nitrogen levels (1, 2/3, 1/3, 0 nitrogen) were conducted; plant growth, fruit yield and quality were surveyed; and comprehensive quality and net profit were evaluated. The results show that water and nitrogen deficit decreased plant growth, evapotranspiration and yield while increasing production efficiency and fruit comprehensive quality. An antagonism effect from water and nitrogen application was found in tomato yield, organic acid, solids acid ratio, vitamin C and lycopene, whereas synergistic impact was observed in total soluble solids content. Water deficit had more significant effect on tomato yield and fruit quality parameters compared with that of nitrogen deficiency. Synthesizing the perspectives of yield, quality, resource productivity, market price index and profits, 1/3 full irrigation and 2/3 full nitrogen was the best strategy and could be recommended to farmers as an effective guidance for tomato production.