Contaminants of emerging concern (CECs) pose persistent and bioaccumulative risks to ecosystems and human health, making the elucidation of their fate critical for effective pollution control. However, tracking their transformation in complex environmental matrices remains analytically, mechanistically, and interpretively challenging. Multi-element compound-specific isotope analysis (ME-CSIA) offers a powerful means of tracking the fate of CECs under complex environmental conditions. ME-CSIA addresses this challenge by measuring isotope shifts of several elements within individual pollutant molecules. These multidimensional isotope fingerprints can distinguish contaminant sources, identify transformation pathways, and quantify degradation even when concentration data alone are ambiguous. This review summarizes the methodological history of ME-CSIA for CECs: from the precise yet element-limited gas or liquid chromatography coupled to isotope-ratio mass spectrometry to the advanced gas chromatography–multi-collector inductively coupled plasma mass spectrometry and Orbitrap mass spectrometry. We highlight its use in source apportionment, abiotic and biotic transformation studies, and field-scale assessment, and we discuss current limitations in sensitivity, matrix interference, isotope reference materials, and data interpretation. Future progress hinges on bridging the gap between laboratory potential and natural application. Research priorities should be given to standardization of emerging techniques and optimization of pretreatment strategies for effective in situ monitoring, both of these are essential to understanding the environmental fate and advancing the regulatory management of CECs.