Mineral elements play a crucial role in plant growth and development.  Ensuring the proper supply of these elements in the soil to maintain the optimum range within plants is necessary for achieving optimal fruit yield and quality.  Unfortunately, the application of NPKCaMg fertilizers to fruit trees is often either insufficient or excessive, leading to environmental degradation and reduced fruit yield and quality.  To assess the impacts of different fertilizers on the biological traits of grapes and their responses to nutritional elements, Merlot grapevines were subjected to multi-nutrient fertilization over four consecutive growing seasons from 2018 to 2021 in Penglai District, Yantai, China.  Principal component analysis revealed that the T11 treatment, consisting of N₃P₃K₁Ca₂Mg₄, was the most suitable fertilizer type and application design among the treatments.  The application of T11 resulted in a significantly lower (24.29–35.20%) fertilizer usage, and it resulted in increases in several important traits such as 100-grain weight (HGW), number of seeds (SN), total soluble solids (TSS), total seed phenols (SP), seed flavanols (SFI), and seed tannins (ST) by 3.28–12.84%, 3.76–20.03%, 1.11–14.95%, 2.16–23.69%, 11.00–32.78%, and 1.07–23.35%, respectively, compared to the T14 (N₄P₂K₃Ca₁Mg₄), T16 (N₄P₄K₁Ca₃Mg₂), T13 (N₄P₁K₄Ca₂Mg₃), and T15 (N₄P₃K₂Ca₄Mg₁) treatments.  Flowering and fruiting processes exhibited a considerable demand for NPK, with higher requirements for K and B during fruit growth and development compared to the other macroelements and micronutrients, respectively.  Excessive K in soil enhanced the competitive inhibition of Ca uptake by Merlot grapevines.  The optimal ranges of mineral element contents for total peel phenols (PP), peel flavanols (PFI), total peel flavonoids (PFD), total seed phenols (SP), and seed tannins (ST) were primarily influenced by grape variety and nutritional analysis method.  In conclusion, the careful selection of NPKCaMg fertilizer and its precise application to soil at an optimum range of mineral elements is critical for grapevine growth and development.