Crop microbiomes are the key factors that decide plants’ health and productivity. The association of microbiomes with the plants significantly affects the end product. Nanoparticles enhanced agricultural productivity, but their interaction with the crop microbiomes and with the host plant directly or indirectly modulates the microbial composition and their activities. They also play their role in changing the soil’s physical and chemical properties. NPs are biphasic in nature, which means their role as either beneficial or phytotoxic is linked with the type of NPs, the concentration of NPs, the type of host species, soil type, and other environmental factors. NPs contain reactive surfaces, and due to their small size, they are used as fungicides, bactericides, and nanofertilizers. Different products, like nanofertilizers, nanopesticides, and encapsulated nanocarriers, have been developed. They are effective for the removal of weeds, pathogens, and insects and enhance the production of crops but sometimes create toxicities in the environment. This chapter summarizes the effects of commonly used NPs on plant microbiomes, including bacteria, viruses, and mycorrhiza. They change the microbial composition, diversity, and soil properties as well. The positive and negative interactions of NPs with the microbes have been discussed in detail.