The increasing global demand for food necessitates improved nutrient management strategies to enhance crop productivity while minimizing environmental impacts. Nutrient interactions in soil and plants play a crucial role in determining nutrient use efficiency (NUE) and crop yield. This paper explores the mechanisms of nutrient synergy and antagonism, emphasizing their implications for sustainable agriculture. Synergistic interactions, such as co-enhancement of solubility, nutrient transport facilitation, and enzyme activation, optimize nutrient uptake and utilization. In contrast, antagonistic interactions, including competitive ion uptake and chemical precipitation, lead to nutrient deficiencies and reduced crop productivity. The article highlights the importance of balanced nutrient application, site-specific fertilization and soil pH management to mitigate nutrient imbalances. Effective strategies such as soil testing, 4R nutrient stewardship, integrated nutrient management (INM), and precision agriculture using IoT-based technologies are essential for maintaining soil fertility and enhancing crop yields. Understanding nutrient interactions and implementing evidence-based fertilization practices will support sustainable agricultural intensification and long-term food security.