Heavy metal and metalloid contamination in soils is detrimental to productivity and food safety, primarily due to the increased bioavailability of toxic elements such as cadmium (Cd), lead (Pb), chromium (Cr), arsenic (As), and aluminium (Al). In Triticum aestivum, excessive exposure to these metals impairs root development, nutrient uptake, photosynthetic efficiency, and redox balance, leading to oxidative damage, enzyme inhibition, altered carbon metabolism, and yield reductions that can exceed 50% under severe stress, whilst also increasing dietary health risks through toxic element accumulation in grains. This chapter reviews recent advances in understanding the physiological, biochemical, and molecular mechanisms underlying metal tolerance in wheat, highlighting the roles of antioxidant defence systems, the ascorbate–glutathione cycle, phytochelatin- and metallothionein-mediated chelation, and vacuolar sequestration as primary detoxification strategies. The functions of key transporter families, including NRAMP, HMA, ZIP, ABC, YSL, VIT, and MATE, as well as regulatory transcription factors such as NAC and WRKY, are examined in relation to metal uptake, distribution, and exclusion. Advances in quantitative trait locus (QTL) mapping and genome-wide association studies (GWAS), particularly the identification of major loci such as Cdu-B1 (TdHMA3-B1) that control grain Cd accumulation, have facilitated marker-assisted and genomics-assisted breeding for low-metal cultivars. The integration of conventional screening, high-throughput phenotyping, genomic selection, multi-omics approaches, and CRISPR/Cas-mediated genome editing is accelerating the development of wheat genotypes with metal tolerance, high yield, and grain safety, whilst the strategic use of landraces, wild relatives, synthetic hexaploids, and alien introgressions further broadens the genetic base for durable tolerance and the breeding of cultivars suited to contaminated agroecosystems.