Endophytes as microorganisms residing in plant tissues systemically have emerged as the most critical players in plant-microbe interactions, having significant impacts such as to the evolutionary trajectories and ecological dynamics of host plants. This chapter outlines the complex interplay between the host plants and their endophytes and unveils the evolutionary and environmental factors influencing the symbiosis. One of the factors impacting the endophyte is host specificity, another is co-evolutionary relationship with the plant, and third one is abiotic factors like temperature and nutrient availability. The molecular mechanisms which endophytes use, for example, gene expression of stress responsive genes and secondary metabolite production are very important in building of host plant tolerance to happenings of environmental stresses. High-level methods such as mass spectrometry and molecular networking determine the microbial metabolites as well as their producing organisms. This makes it possible to learn more about the details of the molecular interactions that are sustaining an endophyte-host relationship. Furthermore, the review covers the impact of frontier cultivation techniques in association between symbionts and their impact on sustainable agriculture. Possibilities for the future in this field pay attention to deeper research work about mechanisms of endophyte-mediated stress tolerance and their use in environmental management and crop upgrading.