Heavy metal (HM) stress poses a noteworthy confront in contemporary agronomy, leading to diminished crop yield, impaired quality, and risks to food security. The accumulation of hazardous metals, involving cadmium (Cd), lead (Pb), and arsenic (As), in agricultural soils disrupts plant physiological systems, such as nutrient absorption, photosynthesis, and enzyme functions. This requires the formulation of novel ways for HM stress adaption and alleviation. Metal and metal-oxide nanoparticles (NPs), including zinc oxide (ZnO), iron oxide (Fe₂O₃), and titanium dioxide (TiO₂), have emerged as pivotal instruments in sustainable agriculture, providing distinctive physicochemical characteristics that improve stress resilience in crops. NPs operate via several methods, such as the immobilization of HMs, the initiation of antioxidant resistance systems, and the intonation of gene expression associated with stress responses. Their capacity to improve photosynthetic efficiency, increase nutrient bioavailability, and diminish reactive oxygen species (ROS) levels establishes them as efficient agents for mitigating HM toxicity. The synergistic application of NPs, namely the combination of silicon (Si) and selenium (Se)-NPs, has shown improved effectiveness in alleviating stress, underscoring their potential for customized therapies. This chapter offers an in-depth analysis of the consequences of HM stress on crops and the function of metal and metal-oxide NPs in adaptation and mitigation strategies. It explores their methods of action, practical uses, and the challenges related to their use, encompassing environmental issues and cost-effectiveness. Future perspectives highlight the enhancement of nanoparticle formulations and the incorporation of nano-enabled technologies into agricultural practices that ensure sustainability and food security.