Interactions among endophytes and plants are widespread and can vary from neutral or positive or negative. Plants are continually in a functionally dynamic state due to interactions with diverse endophytic microorganisms, which produce various metabolic substances. Through quorum sensing, these substances not only help endophytes to outcompete other host-associated pathogens or microbes but also allow them to overcome the plant immune system. Manifold interactions between endophytic microbiota cause a reflective impact on the host plant functioning and the development of ‘endobiomes,’ by synthesizing chemicals that fill the gap between host and endophytes. Despite the advances in the field, specific mechanisms for the endophytes’ precise methods to modulate plant genome and their effects on host plants remain poorly understood. Deeper genomic exploration can provide a locked away understanding of the competencies of endophytes and their conceivable function in host growth and health. Endophytes also can modify host metabolites, which could manipulate plants’ growth, adaptation, and proliferation, and can be a more exciting and puzzling topic that must be properly investigated. The consequence of the interaction of endophytes on the host genome was analyzed as it can help unravel the gray areas of endophytes about which very little or no knowledge exists. This review discusses the recent advances in understanding the future challenges in the emerging research investigating how endosymbionts affect the host’s metabolism and gene expression as an effective strategy for imparting resistance to biotic and abiotic challenges.