Water dropwort (Oenanthe javanica (Blume) DC.) is an important vegetable crop. Nutrient liquid culture has become an important cultivation method in the production of water dropwort. However, the effects of different nutrient solution cultivation methods on the growth and quality of water dropwort remains unclear. In this study, to screen the most suitable nutrient solution formula for the cultivation of water dropwort, the effects of different nutrient solution formulas (Hoagland, Cooper, Dutch greenhouse, Garden-style, Yamasaki and SCAU) on plant physiological and quality characteristics are investigated. The plant height, root length, water content (%), distribution rate of dry matter (%), chlorophyll, VC, flavonoid, total phenolic, DPPH and dietary fiber of water dropwort under different nutrient solutions were determined. According to the analytic hierarchy process (AHP) of the growth index and quality index of water dropwort under different nutrient solutions, the Yamazaki nutrient solution was considered to be the most suitable nutrient solution formula for water dropwort. To further confirm the differences of water dropwort under nutrient solution culture and soil culture, the broadly targeted metabolomics were performed. A total of 485 metabolites were detected in water dropwort under optimal nutrient solution and soil cultivation. Metabolomics analysis showed that flavonoids were the most abundant differential accumulated metabolites, and most flavonoids were up-regulated. A qRT-PCR assay indicated that the structural genes of the flavonoid biosynthesis pathway (PAL, C4H, CHS, CHI, F3H, DFR, UFGT) were significantly higher under the Yamasaki nutrient solution treatment. The current study provided a theoretical basis and technical guidance for the nutrient solution cultivation of water dropwort. Meanwhile, this study provides new insights into the study of flavonoids in water dropwort.