The advent of Comprehensive Two-dimensional Gas Chromatography (GC × GC) as a practical and accessible analytical tool had a considerable impact on analytical procedures associated to the so-called “omics” sciences. Specially when GC × GC is hyphenated to mass spectrometers or other multichannel detectors, in a single run it is possible to separate, detect and identify up to thousands of metabolites. However, the resulting data sets are exceedingly complex, and retrieving proper biochemical information from them demands powerful statistical tools to deal effectively with the massive amount of information generated by GC × GC. Nevertheless, the obtention of results valid on a chemical and biological standpoint depends on a deep understanding by the analyst of the fundamentals both of GC × GC and chemometrics. This review focuses on the basics of contemporary, fundamental chemometric tools applied to proccessing of GC × GC obtained from metabolomic, petroleomic and foodomic analyses. Here, we described the fundamentals of pattern recognition methods applied to GC × GC. Also, we explore how different detectors affect data structure and approaches for better data handling. Limitations regarding data structure and deviations from linearity are stressed for each algorithm, as well as their typical applications and expected output.