The current fertilizer recommendations for melon plantation have many limitations and exhibit deficiencies regarding future development. Therefore, in this study, the optimal quantities of fertilizer, in terms of the effects of single factors and interaction effects, are studied. There were significant interaction effects between N and P, N and K, P and K; the contents of soluble protein, vitamin C (Vc), and soluble sugar in melon could be improved using the optimal fertilization ratios. The optimal ratio of N:P:K was 2.33:1:3.85, with the amounts of N, P2O5, and K2O, respectively, being 157.5, 67.58, and 260.38 kg/hm2, yielding 8.73 g/kg of soluble protein in melon. The optimal ratio of N:P:K was 2.03:1:3.36, with amounts of N, P2O5, and K2O being 157.50, 77.40, and 260.38 kg/hm2, respectively, yielding 25.32 g/kg Vc content in melon. Finally, the optimal ratio of N:P:K was 1.53:1:3.36, with the amounts of N, P2O5, and K2O being 118.07, 77.40, respectively, and 260.38 kg/hm2, yielding 13.34% soluble sugar content in melon.