Globally, the toxicity of metals and metalloids is increasing, primarily as a result of human activities. Among these, agricultural productivity is impacted by soil contamination. Metals and metalloids have the potential to infiltrate the food chain and undergo biomagnification, which could have concurrent effects on environmental changes and human health. Furthermore, the intake of nutrients, photosynthesis, and cellular metabolism are all impacted by heavy metal contamination, both natural and man-made. Therefore, heavy metal and metalloid toxicity poses significant threats to global agricultural productivity and food security. These toxic elements accumulate in crop plants, leading to oxidative stress, physiological disruptions, and yield losses. To counter these challenges, plants employ various defense mechanisms. This chapter discusses agronomic, transgenic and genome-editing approaches to mitigate metal toxicity. Agronomic interventions, such as soil amendments, biochar application, and microbial inoculation, help mitigate metal toxicity by enhancing nutrient balance and immobilizing toxic elements. Transgenic strategies have enabled the development of metal-tolerant plants through the overexpression of metal-chelating proteins, antioxidant enzymes, and transporters that regulate metal uptake and sequestration. Recent advances in Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)–Cas9 genome editing have provided precise tools for engineering plant tolerance by modifying genes associated with metal detoxification, stress signaling, and root architecture. This chapter explores the integrated application of these strategies to alleviate heavy metal/metalloid-induced toxicity and minimize heavy metal/metalloid accumulation in crops, thereby ensuring sustainable agricultural practices and food safety.