<p>Heavy metals (HMs) and metalloids pose a serious environmental threat due to their persistent toxicity, which adversely affects soil, water, and air quality. Metals such as zinc (Zn), copper (Cu), and nickel (Ni) are essential in trace amounts, but become hazardous at higher concentrations. In contrast, HMs such as lead (Pb), cadmium (Cd), mercury (Hg), and chromium (Cr), along with some metalloids like arsenic (As) and selenium (Se)are highly toxic even at low levels and have serious adverse effects on plants, soil, and agricultural productivity. Plants have developed various sophisticated mechanisms to alleviate HMs and metalloids stress, including structural modifications that restrict metal uptake. They also utilize various intracellular physiological and biochemical mechanisms such as chelation, sequestration, antioxidant defense, and epigenetic modifications to regulate gene expression to enhance tolerance to HMs and metalloids stress. Advances in phytoremediation technologies and the development of genetically modified plants are critical to decontaminating soil and water as well as ensuring food security. Transport proteins and phytohormones play important roles in managing metal stress and maintaining plant health. Integrating these molecular and physiological insights is essential to improve environmental management and agricultural strategies to effectively mitigate HMs and metalloids pollution. Gene expression studies show that HMs and metalloids stress affects the expression of genes involved in metal metabolism, transport, detoxification, and oxidative stress, along with a variety of tissue-specific responses. Integration of genetic, epigenetic, and molecular insights is essential to enhance soil remediation and enhance crop resilience to HMs and metalloids stress. This review summarizes plant responses to HMs and metalloids and highlights integrated physiological, molecular, and biotechnological strategies for their mitigation. Importantly, accumulation of HMs and metalloids in edible plant tissues above permissible limits, as defined by WHO/FAO food safety guidelines, poses serious risks to food safety and human health. Future research should focus on advanced genome-editing tools and microbe-assisted phytoremediation to optimize remediation strategies and promote sustainable agriculture.</p> Graphical Abstract <p></p>