Abstract:With the rapid advancement of single-cell technologies, Single Cell Inductively Coupled Plasma Mass Spectrometry (SC-ICP-MS) has emerged as a key analytical method for quantifying intracellular elemental contents and elucidating cell-to-cell heterogeneity in elemental distribution, owing to its high sensitivity and accuracy. This technique has substantially advanced research on cellular trace elements and the characterization of cellular heterogeneity. This review provides a systematic overview of recent developments in SC-ICP-MS, with a particular focus on innovations in single-cell introduction methods, quantitative calibration strategies, and mass spectrometer optimization. It further summarizes representative applications of SC-ICP-MS in biomedicine, environmental toxicology, and studies of nanoparticle uptake at the single-cell level. Together, these insights aim to offer methodological guidance and perspectives for future developments in this rapidly evolving field.