Heavy metal contamination of soil and water has become a major constraint to crop productivity and quality, especially with increasing population and food demand. Plants respond to heavy metal stress through various molecular, biochemical, and physiological mechanisms, which can enhance crop productivity. Recent advances in biological sciences, including metabolomics, transcriptomics, proteomics, and ionomics, have helped characterize the mechanisms involved in heavy metal tolerance. This review discusses the role of metabolites, trace elements, transcription factors, stress-inducible proteins, and plant hormones in heavy metal tolerance. It also provides an overview of strategies used by metal-accumulating plants, known as metallophytes. Heavy metals exert toxicity through several mechanisms, including competition with nutrient cations, direct interaction with sulfhydryl groups, displacement of essential cations, and generation of reactive oxygen species (ROS). Plants respond to heavy metal stress by developing strategies such as root growth regulation, membrane protection, and metal sequestration. Hyperaccumulators, which can absorb and store large amounts of heavy metals, have been studied extensively. These plants translocate metals from roots to shoots and sequester them in vacuoles, reducing toxicity. The detoxification of heavy metals involves various transporter proteins, including ABC, CDF, HMA, and NRAMP transporters, which help in transporting metals into vacuoles. Organic acids and amino acids also play a role in chelating metals and reducing their toxicity. Antioxidant defense systems, including enzymes like SOD, CAT, and APX, and non-enzymatic antioxidants like glutathione and α-tocopherol, are crucial in mitigating oxidative stress caused by heavy metals. The use of "omics" tools, such as metabolomics, transcriptomics, proteomics, and ionomics, has provided insights into the molecular mechanisms underlying heavy metal tolerance. These tools help in understanding the complex interactions between plants and heavy metals, and can be used to develop crops with enhanced tolerance to heavy metal stress. The review highlights the importance of these approaches in improving crop productivity and reducing the risk of heavy metal contamination in food chains.Heavy metal contamination of soil and water has become a major constraint to crop productivity and quality, especially with increasing population and food demand. Plants respond to heavy metal stress through various molecular, biochemical, and physiological mechanisms, which can enhance crop productivity. Recent advances in biological sciences, including metabolomics, transcriptomics, proteomics, and ionomics, have helped characterize the mechanisms involved in heavy metal tolerance. This review discusses the role of metabolites, trace elements, transcription factors, stress-inducible proteins, and plant hormones in heavy metal tolerance. It also provides an overview of strategies used by metal-accumulating plants, known as metallophytes. Heavy metals exert toxicity through several mechanisms, including competition with nutrient cations, direct interaction with sulfhydryl groups, displacement of essential cations, and generation of reactive oxygen species (ROS). Plants respond to heavy metal stress by developing strategies such as root growth regulation, membrane protection, and metal sequestration. Hyperaccumulators, which can absorb and store large amounts of heavy metals, have been studied extensively. These plants translocate metals from roots to shoots and sequester them in vacuoles, reducing toxicity. The detoxification of heavy metals involves various transporter proteins, including ABC, CDF, HMA, and NRAMP transporters, which help in transporting metals into vacuoles. Organic acids and amino acids also play a role in chelating metals and reducing their toxicity. Antioxidant defense systems, including enzymes like SOD, CAT, and APX, and non-enzymatic antioxidants like glutathione and α-tocopherol, are crucial in mitigating oxidative stress caused by heavy metals. The use of "omics" tools, such as metabolomics, transcriptomics, proteomics, and ionomics, has provided insights into the molecular mechanisms underlying heavy metal tolerance. These tools help in understanding the complex interactions between plants and heavy metals, and can be used to develop crops with enhanced tolerance to heavy metal stress. The review highlights the importance of these approaches in improving crop productivity and reducing the risk of heavy metal contamination in food chains.