Endophytes serve as valuable reservoirs of bioactive compounds with a wide-range of applications. Investigating these compounds not only enhances our comprehension of ecological dynamics but also holds immense potential for developing innovative products with agricultural, medicinal, and industrial relevance. The ongoing exploration of endophyte diversity, coupled with understanding the ecological functions of bioactive compounds, presents avenues for novel discoveries and applications. Omics methodologies, which include genomics, transcriptomics, proteomics, and metabolomics, are crucial in revealing the characteristics and potential applications of endophytes. By incorporating omics techniques, a broader range of molecular information can be captured. Multi-omics methodologies are essential for investigating the symbiotic relationship. These omics approaches are instrumental in deciphering the intricate interactions between endophytes and their host plants, offering valuable insights into the molecular mechanisms underpinning these associations and the possible applications. This book chapter offers a comprehensive overview on how major “omics” techniques contribute to the advancement of our knowledge about endophytes e.g., bacteria (Pseudomonas, Bacillus, Burkholderia, Stenotrophomonas, Micrococcus, Pantoea, Microbacterium, etc) and fungi (Aspergillus Alternaria, Fusarium, Trichoderma, Penicillium, Piriformospora, etc) and their various roles e.g., stress-tolerance genes to withstand plant-induced oxidative stress; release of bioactive secondary metabolites (e.g., antibiotics, antifungals); and activation of secretion systems (T3SS, T6SS) for host colonization and immune evasion . Moreover, the advancement of meta-omics technologies is revolutionizing our understanding of the microbial communities linked to plants, uncovering the mutual evolution of host plants and endophytes.