Feeding the world's growing population requires continuously increasing crop yields with less fertilizers and agrochemicals on limited land. Focusing on plant belowground traits, especially root-soil-microbe interactions, holds a great promise for overcoming this challenge. The belowground root-soil-microbe interactions are complex and involve a range of physical, chemical, and biological processes that influence nutrient-use efficiency, plant growth and health. Understanding, predicting, and manipulating these rhizosphere processes will enable us to harness the relevant interactions to improve plant productivity and nutrient-use efficiency. Here, we review the recent progress and challenges in root-soil-microbe interactions. We also highlight how root-soil-microbe interactions could be manipulated to ensure food security and resource sustainability in a changing global climate, with an emphasis on reducing our dependence on fertilizers and agrochemicals.