Crop plants are highly dependent on nutrients applied as fertilizers to reach high yields. However, modifications of environmental conditions due to climate change directly influence nutrient uptake, utilization, and homeostasis in plants. Increasing nutrient use efficiency is a crucial factor for ensuring sustainability in agriculture that is facing its major challenges of improving crop productivity and food security in the era of climate change. In this chapter, we describe genetic engineering approaches and molecular strategies to enhance nutrient uptake, utilization, and homeostasis in plants for improving crop yield and quality.