Heavy metals in the soil inhibit plant growth, which significantly reduce the crop yield and quality. Natural Resistance-Associated Macrophage Proteins (NRAMP) are widely distributed on the plasma and vacuolar membranes of plant roots, stems, and leaves. The NRAMP gene family plays a crucial role in modulating plant heavy-metal uptake, sequestration, distribution, and translocation, while the molecular evolution and mechanisms underlying these processes remain unclear. Here, we reviewed recent progress on plant NRAMP genes, focusing on their structural characteristics and functions in the absorption, transport, accumulation, and detoxification of various heavy metals. Furthermore, we performed an evolutionary analysis of NRAMP in green plants, indicating expansion and tandem duplication in ferns. In addition, their key amino acid sequences and secondary structures were highly conserved across plant species. The expression of diverse tissue showed that NRAMP genes displayed distinct spatial regulation in the leaves and roots. We also explored the underlying molecular mechanisms and regulatory pathways by which NRAMP genes influence heavy metal uptake. Therefore, by integrating structural conservation, molecular evolution, tissue- and single-cell expression patterns, ion-stress-responsive expression, regulatory pathways, and the Cd–Mn nutrient–toxin trade-off, this review provides a framework for identifying unresolved NRAMP functions and for guiding future strategies in low-heavy-metal crop breeding, metal homeostasis engineering, and phytoremediation.