This study was conducted to identify nutritional balance of multiple nutrients (N, P, K, Ca, Mg, Fe, Mn, Zn and Cu) of wheat grown in Sahl El-Tina, Egypt, using compositional nutrient diagnosis model (CND). Additionally, significant nutrient interactions in wheat using principal component analysis of the computed indexes were assessed. The soils in the study area could be classified into five mapping units, depending on soil texture and profile depth. Moreover, high contents of available K, Mg, Fe, Mn and Cu were detected in most of the soils. Wheat yields were substantially different that ranged from about 3371 to 5925 kg ha-1. The CND indexes of wheat grain for N, K, Ca and Zn in the study area revealed negative imbalance with average values of -1.75, 5.94, -5.03 and -1.25, respectively. Conversely, the CND indexes of P, Mg, Fe, Mn and Cu revealed positive imbalance with average values of 1.13, 2.29, 4.70, 2.05 and 0.46, respectively. These results indicate that K is the most deficient nutrient in wheat, followed by Ca, N and Zn, whereas Fe is the most excessive nutrient, followed by Mg, Mn, P and Cu. Through the principal component analysis of the CND indexes, synergistic interactions of N-P and Mg-Mn, and antagonistic interactions of K-Mg, K-Mn, NCa, P-Ca and Fe-Zn were evidenced. This study revealed that the decline in the productivity of wheat in Sahl ElTina caused by nutrient imbalance associated with multinutrient deficiency (K, Ca, N and Zn) and multi-nutrient excess (Fe, Mg, Mn and P).