Natural and anthropogenic causes are continually growing sources of metals in the ecosystem; hence, heavy metal (HM) accumulation has become a primary environmental concern. HM contamination poses a serious threat to plants. A major focus of global research has been to develop cost-effective and proficient phytoremediation technologies to rehabilitate HM-contaminated soil. In this regard, there is a need for insights into the mechanisms associated with the accumulation and tolerance of HMs in plants. It has been recently suggested that plant root architecture has a critical role in the processes that determine sensitivity or tolerance to HMs stress. Several plant species, including those from aquatic habitats, are considered good hyperaccumulators for HM cleanup. Several transporters, such as the ABC transporter family, NRAMP, HMA, and metal tolerance proteins, are involved in the metal acquisition mechanisms. Omics tools have shown that HM stress regulates several genes, stress metabolites or small molecules, microRNAs, and phytohormones to promote tolerance to HM stress and for efficient regulation of metabolic pathways for survival. This review presents a mechanistic view of HM uptake, translocation, and detoxification. Sustainable plant-based solutions may provide essential and economical means of mitigating HM toxicity. [Display omitted] • Increasing sources of heavy metals influencing the uptake and translocation in plants • Rhizosphere acts as the gatekeeper, i.e. first line of defense • Efficient induction of detoxification mechanism decides fate of plant survival • Omics approaches reveals key regulators associated with plant metal tolerance • Plant species can act as hyperaccumulator for environmental clean-up [ABSTRACT FROM AUTHOR]