The plant genome and its microbiome act together to enhance survival and promote host growth under various stresses. Plant microbiome plays an important role in plant productivity via a multitude of mechanisms including provision of nutrients and resistance against different biotic and abiotic factors. However, the molecular mechanisms responsible for plant microbiome interactions remain largely unknown. Nevertheless, gaining a deeper understanding of the plant genetic traits driving microbiome recruitments and assembly holds the potential to greatly enhance our capacity to utilize the microbiome effectively, leading to sustainable improvements in agricultural productivity and produce quality. This article explores the mutual influence of specific plant genes in modulating the rhizosphere (area around plant roots) microbiome, and how this rhizosphere microbiome impacts the plant genes, ultimately enhancing plant health and productivity. It further examines the effects of various rhizosphere microbiota, including Bacillus, Pseudomonas, Azospirillum, Trichoderma spp., on plant development, immunology and the expression of host functional genes. We conclude that the adoption of a hologenomics approach (i.e., considering both the plant genome and the genomes of all microorganisms colonizing the plant) can significantly advance our understanding of plant resistance and resilience to biotic and abiotic stresses. This approach can offer improved solutions for agronomic challenges in the future. Furthermore, within this context, we identify key knowledge gaps within the discipline and propose frameworks that may be employed in the future to harness plant–microbial interactions effectively, leading to a sustainable increase in farm productivity.