A rapid and sensitive method based on desorption electrospray ionization mass spectrometry (DESI-MS) has been utilized for the detection of chemicals related to cosmetic products without prior preparation. DESI-MS was used to rapidly screen target compounds at ambient conditions, allowing the investigation of surface-bound residues, complex chemical matrices, and components of authentic cosmetic formulations. This high-throughput method routinely achieved low nanogram detection limits, and quantitative ability was demonstrated with decent linearity and precision. Continuous, direct analysis of cosmetic impurities in drinking water matrices was also validated, implementing thermal assistance into the ionization source design to increase overall sensitivity.