Plants and their associated microbiota form a plant holobiont, and interactions among these organisms determine the functioning of the holobiont and the performance of the plant. Furthermore, the degree of interaction between these organisms and various species strongly influences ecosystem functioning. Therefore, any switch in these interactions may profoundly alter the functionality of the ecosystem and its ability to provide goods and services to society. These interactions are highly complex in nature and are less known because of the methodological difficulties associated with understanding the temporal dynamics of these interactions occurring at plant–soil interface “rhizosphere.” As per the available information, plant microbes and their interactions prevent common diseases, fix atmospheric nitrogen, increase the resilience of plants to stress tolerance, enhance physical vigor and robustness, boost the efficiency of nutrient consumption, and provide tolerance to abiotic challenges. Research is progressing to unravel the complexity of the microorganisms involved and their interactions to develop sustainable crop production practices for different regions. However, further studies are needed to understand microbiome interactions and holobiont functioning to manipulate them more effectively to develop sustainable crop production models and overcome environmental consequences. This chapter primarily focuses on plant–microbe interactions and their role in the functioning and sustainability of ecosystems.