Although the skin barrier assumed to be intact and functionally competent effectively limits the transdermal penetration of exogenous substances, the potential for nanoplastics to penetrate this barrier and translocate systemically remains a critical toxicological concern. In this study, we employed radiolabelled 125I-nano-sized polystyrene (125I-nPS) to trace dermal penetration and to observe systemic biodistribution using a chronic dermal exposure model. Transcriptomic analyses revealed upregulation of inflammation and ageing markers in exposed skin. Transcriptomic analyses revealed upregulation of 294 genes and downregulation of 144 genes, including significant increases in TNF-α, IL-6, CD207, MMP-3, and CCL2 (F.C.>2, P < 0.05). Single Photon Emission Computed Tomography (SPECT) / Computed Tomography (CT) imaging and ex-vivo biodistribution of 125I-nPS revealed significantly enhanced lymphatic uptake. SPECT/CT imaging and ex-vivo biodistribution demonstrated lymph node uptake up to 0.31 ± 0.19%ID/g (chronic exposure group), accompanied by systemic dissemination to the thymus and lungs. In the prolonged chronic dermal exposure model, nPS progressively translocated from the skin to the lymph nodes, thymus, lungs, liver, and blood over a 4-week period. Our findings provide direct in-vivo evidence that chronic dermal exposure particularly under conditions simulating prolonged environmental insult can facilitate the systemic dissemination of nPS. These results raise critical concerns regarding potential immune modulation, organ-specific toxicity, and skin ageing associated with long-term environmental exposure to nPS.