The yield, quality, and water–fertilizer use efficiency of crops are important parameters for assessing rational water and fertilizer management. For an optimal water and fertilizer system with respect to the nutrient solution irrigation of greenhouse tomatoes using cultivation substrates, a two-year greenhouse cultivation experiment was conducted from 2022 to 2023. Three drip fertigation treatments (T1, T2, and T3) were implemented in the experiment, where nutrient solutions were supplied when the substrate’s water content reached 60%, 70%, and 80%. The frequency of nutrient solution applications is based on weighing coconut coir strips in the morning and evening at 7:00 to determine the daily water consumption of plants. Nutrient solutions were supplied when the substrate’s water content reached the lower limit, and the upper limit for nutrient supply was set at 100% of the substrate water content. The nutrient solution application was carried out multiple times throughout the day, avoiding the midday heat. The nutrient solution formula used was the soilless tomato cultivation formula from South China Agricultural University. The results show that plant height and the leaf area index rapidly increased in the early and middle stages, and later growth tended to stabilize; the daily transpiration of tomatoes increased with an increase in nutrient solution supply, and it was the greatest in the T3 treatment. Between the amount of nutrient solution application and the number of years, the yield increased with the increase of the amount of nutrient solution, showing T3 > T2 > T1. Although the average yield of the T2 treatment was slightly lower than that of the T3 treatment by 3.65%, the average irrigation water use efficiency, water use efficiency, and partial fertilizer productivity of the T2 treatment were significantly higher than those of the T3 treatment by 29.10%, 19.99%, and 28.89%, respectively (p < 0.05). Additionally, soluble solid, vitamin C, and soluble sugar contents and the sugar–acid ratio of tomatoes in the T2 treatment were greater than those in the other two treatments (p < 0.05). Using the TOPSIS (Technique for Order Preference by Similarity to an Ideal Solution) method, it was concluded that the nutrient solution application rate of 70% can significantly increase water and fertilizer use efficiency and markedly improve the nutritional and flavor quality of the fruit without a significant reduction in yield. This finding provides significant guidance for the high-yield, high-quality, and efficient production of coconut coir-based cultivated tomatoes in greenhouses.