Recent industrialisation has seen an alarming increase in heavy metal pollution, raising the question of how to sustain food production in the presence of heavy metals. Several reviews have addressed the direct and indirect effects of heavy metals on crop physiological and biochemical processes. However, understanding of the physiological and molecular mechanisms requires integrating omic approaches to explore the target mechanism in general in crops, and those insights are still lacking. To date, most of the information related to omic approaches about heavy metals has been sparse and sporadic. This review, by means of examples, attempts to integrate different available proteomic, transcriptomic and genomic approaches in a nutshell along with underlying physiological and molecular mechanisms occurring in crops. Major identified transcription factors (TFs) (MYBs, WRKYs), transgenes (MT2, Nramp6, GSTU3, CIPK, MYB1 and DRE), up-regulated (CAT, SODs, POD and APX), down-regulated (ATPase subunits, Rubisco subunits and photosystem I (PSI) reaction centre) proteins, and miRNA (miR397, miR398a, miR408, OsmiR601 and miR166) for major heavy metals have been summarised. It provides a mode of action of heavy metals and their fate inside the plant. It also elucidates how these omics approaches facilitate in mitigating heavy metal stress and could help in addressing crop tolerance based on these mechanisms. Identifying donors with the aid of novel omic approaches could be useful for the development of HM tolerant crops, promoting future sustainability in heavy-metal-polluted soil and water resources.