Late blight of potatoes, caused by Phytophthora infestans, poses a major challenge to global potato cultivation, resulting in significant economic losses and environmental issues due to the widespread application of fungicides. In India, late blight poses a substantial challenge, with historical occurrences dating back to the late nineteenth century, yet gaining widespread attention only after devastating epidemics, such as the 2008 outbreak in South India, resulting in a complete yield loss of up to 100%. The rapid emergence of fungicide-resistant strains further exacerbates management difficulties. To overcome these challenges, increasing attention has been given to leveraging the plant’s microbiome as a sustainable strategy for disease management. Several endophytic microorganisms have been well exploited for managing various fungal, bacterial and viral pathogens. Due to their versatile nature and wider adaptability, Bacillus species have emerged as promising candidates for managing late blight. These endophytic bacteria not only inhibit P. infestans but also improve plant growth and induce systemic resistance during various biotic and abiotic stresses. Understanding these interactions is essential for unraveling the function of transcriptional regulators in various signaling cascades and enhancing plant defense strategies. Pattern recognition receptors (PRRs) activate pattern-triggered immunity (PTI) upon the detection of microbial-associated molecular patterns (MAMPs), resulting in downstream responses, including reactive oxygen species (ROS) production and defense gene activation. Furthermore, the characterization of biomolecules by Bacillus species during the interactions with P. infestans holds a promising approach for developing novel biocontrol strategies. Molecular docking and simulation techniques provide crucial insights into the interactions between bacterial biomolecules and pathogen targets, facilitating the discovery of potent antimicrobial compounds. Further, genomic analysis of Bacillus strains provides a foundation for understanding their genetic diversity and identifying genes associated with anti-oomycete activity. Integrating transcriptomic studies with field evaluations of bioformulations offers a comprehensive approach to elucidate the efficacy of bacterial endophytes in managing the late blight of potatoes. This chapter delves into the potential of bacterial endobiome-mediated induction of in-planta resistance as a sustainable strategy for late blight management, highlighting the molecular mechanisms underlying the activation of defense response.