The assessment of a multitude of organic xenobiotics at ultra-trace levels (< 10 ng mL ) in exposome research can be achieved by liquid chromatography coupled to mass spectrometry (LC-MS). Recent advances in analytical instrumentation has expedited the detection of trace levels of xenobiotics in human tissues and bio-fluids. Thus, an improved quantitative assessment of the chemical burden of an individual is now feasible. While non-targeted, high-resolution methods are proposed as the future key technology for exposomic research; currently, targeted methods employing triple quadrupole instrumentation still provide higher sensitivity, linearity and reduced data processing needs . The correlation of comprehensive biomonitoring data at a population level with epidemiological data provides a new approach to conceptualize and unravel the contribution of chemicals to the development of disease and may enable individualized treatments for highly exposed patients in the context of precision medicine. Moreover, such information can support informed policy making to protect, in particular, susceptible demographics from adverse chemical exposures via precision prevention (Figure ) to, e.g., endocrine-disrupting phthalates and toxic perfluorinated alkylated substances (PFAS) .