Nitrogen (N), phosphorus (P), sulfur (S), zinc (Zn), and iron (Fe) are some of the vital nutrients required for optimum growth, development, and productivity of plants. The deficiency of any of these nutrients may lead to defects in plant growth and decreased productivity. Plant responses to the deficiency of N, P, S, Fe, or Zn have been studied mainly as a separate event, and only a few reports discuss the molecular basis of biological interaction among the nutrients. Macro-nutrients like N, P, and/or S not only show the interacting pathways for each other but also affect micro-nutrient pathways. Limited reports are available on the investigation of two-by-two or multi-level nutrient interactions in plants. Such studies on the nutrient interaction pathways suggest that an MYB-like transcription factor, phosphate starvation response 1 (PHR1), acts as a master regulator of N, P, S, Fe, and Zn homeostasis. Similarly, light-responsive transcription factors were identified to be involved in modulating nutrient responses in Arabidopsis. This review focuses on the recent advances in our understanding of how plants coordinate the acquisition, transport, signaling, and interacting pathways for N, P, S, Fe, and Zn nutrition at the molecular level. Identification of the important candidate genes for interactions between N, P, S, Fe, and/or Zn metabolic pathways might be useful for the breeders to improve nutrient use efficiency and yield/quality of crop plants. Integrated studies on pathways interactions/cross-talks between macro‐ and micro-nutrients in the agronomically important crop plants would be essential for sustainable agriculture around the globe, particularly under the changing climatic conditions.