Sustainable farming aim is to propagate crops for production of foods and other products in a manner that preserves human health while the environment is also protected from deleterious effects of conventional farming practices. Soil and plants health is promoted by many beneficial microorganisms that are natural inhabitants of the soil. Microorganisms have been documented to fix nitrogen, solubilize nutrients (such as potassium and phosphorus), and produce plant growth regulators (auxin, gibberellin, indole-3 acetic acid and cytokines). Some soil microbes serve as biocontrol agents in sustainable farming either by antagonistic activities against plants pathogens in competing for nutrients, by parasitism, or by production of substances like antibiotics, siderophores, enzymes and volatile compounds. Others aid plants to resist pathogens by improving the plants immune system. Bioinoculants have been successfully used to improve the yield of crops like maize, millet, cowpea and tomatoes, while there are evidences of these plants growth promoting bacteria (PGPB) aiding crops in pots and on field studies to tolerate abiotic stress conditions like drought and high salinity using various mechanisms, to produce higher growth performances than plants in non-stress conditions. New technological innovations like production of biostimulants, incorporation of nano-particles into bioinoculants and utilization of meta-omicsOmics protocols are emerging which have generated greater interests in the use of bioinoculants in sustainable agriculture. However, further studies on the environmental impact and safety of use of these genetically enhanced soil microbes will be required. This chapter aims to provide current information on the use of knowledge on plant-soil microbiome interactions in sustainable agriculture as a potential wealth creation means in commercial food production. It explored the various mechanisms employed by PGPMs in improving agricultural productivity for sustainable food production, and examined recent trends in the studies of soil microbial communities which are helping in developing highly effective bio-inoculants that are economically and environmentally sustainable. Commercial production of bio-inoculants is advocated on wide scale to stimulate accessibility by farmers for promoting sustainable agriculture in attaining global food security and environmental safety.