Different from the traditional irrigation optimization model based only on the water production function, in this study, we explored the water–yield–quality–benefit relationship and established a general irrigation scheduling optimization framework. To establish the framework, (1) an artificial neural network coupled with ensemble empirical mode decomposition (EEMD-ANN) is used to decompose the original price time series into several subseries and then forecast each of them; (2) factor analysis and a technique for order of preference by similarity to ideal solution (FA-TOPSIS), as an integrated evaluation method, is used to comprehensively evaluate the fruit quality parameters; and (3) regression analysis is used to simulate water-yield and water-fruit quality relationships. The model is applied to a case study of greenhouse tomato irrigation schedule optimization. The results indicate that EEMD-ANN can improve the accuracy of price forecasting. Jensen and additive models are selected to simulate the relationships of tomato yield and quality with water deficit at various stages. Besides, the model can balance the contradiction between higher yields and better quality, and optimal irrigation scheduling is obtained under different market conditions. Comparison between the developed model and a traditional modeling approach indicates that the former can improve net benefits, fruit quality, and water use efficiency. This model considers the economic mechanism of market price changing with fruit quality. Forecasting and optimization results can provide reliable and useful advices for local farmers on planting and irrigation.