To collect a complete dataset regarding the occurrence of organic substances in groundwater, this study presents the examination of 66 organic contaminants in the groundwater of overseas departments, including pesticides, pharmaceutical compounds, hormones and some industrial substances. The selective and sensitive analytical methods are described. These techniques begin with solid-phase extraction (SPE) followed by analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-ToF-MS). The paper summarises the analytical results from 40 sampling points collected during two campaigns in Guadeloupe, Martinique, Reunion, Mayotte and Guiana, representing 80 samples. Of the 66 target substances, 36 were determined at least once. Among the most frequently detected are bisphenol A (frequency, 96%; max., 7,400 ng/L), caffeine (frequency, 91%; max., 1,240 ng/L), pentachlorophenol (frequency, 55%; max., 418 ng/L), and carbamazepine (frequency, 56%; max., 22 ng/L). The results do not put in evidence that the origin of the sample or climatic characteristics of these regions influence the dilution and release of micropollutants.