In order to explore the comprehensive regulation of growth, yield and quality of cherry tomatoes by multifactor coupling of water and fertilizer, the optimal combination of water and fertilizer factors was obtained. The orthogonal rotation combination design was carried out with the amounts of irrigation, applied N, applied K2O and applied CaO as test factors, and the multilevel fuzzy evaluation method was used to comprehensively evaluate the four factors and 14 subfactors for characterization of cherry tomatoes’ growth. Finally, the regulation model of water and fertilizer multifactor on the comprehensive growth of cherry tomatoes was constructed. The results showed that when other factors were at the intermediate level, the comprehensive growth of cherry tomatoes showed a linear relationship with the increase of irrigation amount. With the increase of N application rate, K2O application rate and CaO application rate, the parabolic relationship of the opening was downward. The interaction had a negative interaction effect between the amount of irrigation and the amount of K2O application and CaO application. Among the multifactor coupling effects, the irrigation, N, K2O and CaO coding value were 1.682, 0, -0.744 and -1.223, respectively, which was more conducive to the comprehensive growth of cherry tomatoes; for different levels of CaO application, the irrigation, N, K2O and CaO coding value were 1.682, 0.521, 0.071 and -1, respectively, which was most conducive to the comprehensive growth of cherry tomatoes. Finally, irrigation volume was the amount of water needed to replenish to the upper irrigation limit of 91.34%~100%, the amount of N applied was 12.26~13.50g/plant, the amount of applied K2O was 2.92~5.13g/plant, the amount of applied CaO was 2.69~4.39g/plant, the multilevel fuzzy comprehensive evaluation value had the optimal interval, which was most beneficial to the comprehensive growth of cherry tomatoes. 