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Anthropogenic emissions, particularly from industrial and agriculture activities, have significantly elevated the concentrations of highly toxic Heavy Metals (HMs), such as lead (Pb), cadmium (Cd), and arsenic (As), in the soil, leading to their accumulation in plants. These HMs, when exceeding toxicity thresholds (e.g., Pb >10 mg/kg, Cd >0.5 mg/kg, As >1 mg/kg), disrupt the plant physiology and metabolism. To mitigate this toxicity, plants employ diverse detoxification and sequestration strategies, including mycorrhizal associations, root exudates, cellular compartmentalization, and the production of organic acids, phytochelatins, metallothioneins, proline, stress proteins, and plant hormones. This review aims to critically examine the molecular mechanisms by which key crop plants, such as rice, wheat, maize, and other higher plants, sequester these primary heavy metal contaminants. Additionally, it highlights the role of nanotechnology in enhancing plant resistance and facilitating nano-bioremediation under HMs stress conditions. This review provides valuable insights into innovative clean-up strategies for agriculturally important crops by exploring nanoparticle -mediated remediation mechanisms.