Background and aims <p>Soil contamination with heavy metals (HMs) is a major threat to agricultural productivity, ecosystem health, and food safety. Sweet potato (<i>Ipomoea batatas</i>) accumulates HMs in roots and tubers, affecting crop quality and its phytoremediation potential. This review summarizes molecular and physiological mechanisms of HM uptake, transport, sequestration, detoxification, and tolerance. It also highlights research gaps, particularly in transporter kinetics and cultivar-specific tolerance, and suggests priorities for future work to improve phytoremediation and food safety.</p> Results <p>This review integrates knowledge on HM uptake pathways in sweet potato, including apoplastic and symplastic transport. These processes are mediated by zinc/iron-regulated transporter-like proteins (ZIPs), HM adenosine triphosphatases (HMAs), and metal tolerance proteins (MTPs). Ionic mimicry allows HMs to enter cells, which are detoxified via vacuolar storage, chelation with metallothioneins and phytochelatins, and conjugation by glutathione S-transferases (GSTs). Sweet potato mitigates oxidative stress through enzymatic antioxidants (superoxide dismutase, catalase, peroxidase, ascorbate peroxidase) and non-enzymatic antioxidants (glutathione, ascorbate, tocopherols). Stress-related gene expression is regulated by transcription factors such as basic leucine zipper (bZIP), myeloblastosis (MYB), WRKY-domain containing (WRKY), and NAC (NAM-ATAF-CUC2).</p> Conclusion <p>Despite progress in understanding HM tolerance, food safety remains a concern because HMs can accumulate in edible tissues. CRISPR-based genome editing and agronomic practices, including biochar amendment, intercropping, and genotype screening, offer opportunities to develop low HM-accumulating or tolerant cultivars. Further studies on transporter kinetics, transcriptional regulation, and cultivar-specific tolerance are needed to improve the effectiveness and safety of these strategies.</p> Highlights <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Studied molecular mechanisms of heavy metal uptake and detoxification in sweet potato.</p> </ItemContent> <ItemContent> <p>Described importance of heavy metals transporter genes and chelators.</p> </ItemContent> <ItemContent> <p>Explained transcriptional and antioxidant resistance to heavy metals stress.</p> </ItemContent> <ItemContent> <p>Highlighted the role of sweet potato in food safety and phytoremediation of heavy metals.</p> </ItemContent> </UnorderedList></p> Graphical abstract <p></p>