Strict regulations including risk assessment, labeling, traceability and marketing have been established due to the controversial safety aspects of genetically modified organisms (GMOs).One of the main polemic issues associated with GMOs safety are the possible unintended effects, defined as effects that go beyond the primary expected effects of the genetic modification. In order to effectively investigate the potential adverse effects on the human health, including the existence or not of unintended effects, new analytical tools are needed to facilitate comprehensive compositional studies of GMOs. In this context, profiling technologies have the potential to provide valuable information regarding GMOs composition that can be useful for characterization, traceability and even GMO detection. In this chapter, the application of the main -omics technologies (transcriptomics, proteomics, and metabolomics) in combination with bioinformatics and chemometrics tools to GMO profiling are discussed.