The union of plant microbiome science and nanotechnology offers a revolutionary path to sustainable agriculture and enhanced plant health. This chapter addresses the diversity, structure, and role of plant-associated microbial communities’ rhizosphere, phyllosphere, and endosphere microbiota and highlights their crucial roles in plant growth, disease resistance, and ecological adaptation. Functional benefits of the microbiome are also enhanced by advances in multi-omics technologies, through which microbial host interactions and symbiotic processes can be viewed in a holistic manner. At the same time, nanotechnology is revolutionizing modern agriculture with the enhancement of nutrient supply, stress tolerance, and microbial community structure within the soil. This chapter further explores the influence of engineered nanomaterials (NMs) on microbial processes, plant metabolism, and soil characteristics in favor of improved crop yield. The combination of nanomaterials and useful microbes has the potential to bring about precision agriculture with the help of artificial intelligence (AI) and Internet of Things (IoT) platforms for real-time control and monitoring. Finally, the chapter illustrates the promise of solutions based on microbiome and nano-facilitated solutions to address the world’s agrifood problems food security, climate stress, and degraded soil health, making them important tools for achieving resilient and sustainable agrifood systems in the One Health framework.