In forensic chemistry, when investigating seized illicit drugs, the profiling or chemical fingerprinting of drugs is considered fundamental. This involves the identification, quantitation and categorization of drug samples into groups, providing investigative leads such as a common or different origin of seized samples. Further goals of drug profiling include the elucidation of synthetic pathways, identification of adulterants and impurities, as well as identification of a drug’s geographic origin, specifically for plant-derived exhibits. The aim of this state-of-art-review is to present the traditional and advanced analytical approaches commonly followed by forensic chemists worldwide for illicit drug profiling. We discussed numerous methodologies for the physical and chemical profiling of organic and inorganic impurities found in illicit drug. Applications of powerful spectroscopic and chromatographic tools for illicit drug profiling including isotope-Ratio mass spectrometry (IRMS), gas chromatography–mass spectrometry (GC-MS), gas chromatography–isotope ratio mass spectrometry (GC-IRMS), ultra-high-performance liquid chromatography (UHPLC), thin layer chromatography (TLC), liquid chromatography–mass spectrometry (LC-MS) and inductively coupled plasma-mass spectrometry (ICP-MS) were discussed. Altogether, the techniques covered in this paper to profile seized illicit drugs could aid forensic chemists in selecting and applying a suitable method to extract valuable profiling data.