Heavy metal pollution in soil and water leads to serious negative effects to crop productivity, food security, and human health. Agronomic, transgenic, and CRISPR-Cas9 approaches provide effective strategy to minimize heavy metal accumulation in crop plants. Integration of agronomic techniques with molecular and recent biotechnological advancements offers a promising strategy for developing varieties with enhanced tolerance towards heavy metal stress. Agronomic strategies aim to enhance soil quality, limit metal availability, and strengthen plant tolerance toward heavy metal stress through the application of soil amendments, seed priming techniques, and beneficial microbes like rhizobacteria and mycorrhizal fungi. Transgenic approaches involve manipulation of genes included in metal transport, uptake, and sequestration in plant tissues. Overexpression of genes regulating the biosynthesis of metal chelators like phytochelatins, metallothioneins, and antioxidant enzymes like peroxidases, catalases, superoxide dismutase, etc. alleviate heavy metal induced oxidative stress. Activation of metal transporters, signalling molecules, and stress-responsive transcription factors like WRKY, MYB, and bZIP further contribute towards improved plant tolerance. The genes involved in stress-related gene regulatory pathways can be targeted via CRISPR-Cas9 technique to enhance stress tolerance. Targeted gene knockouts decrease heavy metal uptake and translocation, making the crop safer for consumption. This chapter highlights the most promising applications of integrating conventional agronomic practices with advanced genetic and genomic editing tools to develop resilient crop varieties, promoting safer agricultural production and environmental sustainability.