ext-generation sequencing (NGS) technologies are being increasingly evaluated for their feasibility in supporting the current genetically modified organism (GMO) routine detection systems for unauthorized GMO. Depending upon the specific samples under investigation, two categories of NGS approaches can be applied. The whole-genome sequencing approach, on the one hand, requires no prior knowledge, and is suitable for the characterization of samples containing an isolated single GMO. The targeted approach, on the other hand, requires upstream enrichment of a priori known sequences of interest, and allows simultaneous identification of several GMOs, even when present at low concentrations. The application of these NGS approaches to biotech organisms created by genome editing techniques, which are currently not included in the scope of European Union (EU) legislation, is also discussed.