Zinc oxide nanoparticles (ZnO NPs) have garnered significant attention as advanced nanotechnology-based agents for boosting plant resistance to increasing environmental stresses. Because of their distinctive physicochemical characteristics, ZnO NPs enhance nutrient use efficiency, modulate antioxidant machinery, and regulate stress-responsive signalling pathways with higher precision than conventional zinc fertilizers. This chapter reviews the latest progress in applying ZnO NPs to counteract biotic and abiotic stresses, with a focus on their roles in managing reactive oxygen species (ROS), maintaining photosynthetic stability, and regulating osmotic adjustment. The present chapter also explores the antimicrobial mechanisms, including membrane disruption, metabolic interference, and activation of salicylic acid- and jasmonic acid-associated defense pathways, which contribute to increased resistance against fungal and bacterial pathogens. Additionally, the chapter highlights molecular and phytohormonal responses triggered by ZnO NPs, including the upregulation of genes responsible for stress, modification of hormonal homeostasis, and enhancement of systemic acquired resistance. Collectively, this chapter offers a thorough examination of the diverse functions of ZnO NPs in enhancing plant resilience, offering insights into their potential integration into sustainable and resilient agricultural systems.