Cytochrome P450 enzymes (CYPs) represent a diverse family of heme-thiolate proteins involved in the metabolism of a wide range of endogenous compounds and xenobiotics. In recent years, proteomics and metabolomics have been used to obtain a comprehensive insight into the role of CYPs in health and disease aspects. The objective of the present work is to better understand the status of proteomics and metabolomics in CYP research in optimizing therapeutics and patient safety from a personalized medicine approach. The literature used in this narrative review was procured by electronic search of PubMed, Medline, Embase, and Google Scholar databases. The following keywords were used in combination to identify related literature: "proteomics," "metabolomics," "cytochrome P450," "drug metabolism," "disease conditions," "proteome," "liquid chromatography-mass spectrometry," "integration," "metabolites," "pathological conditions." We reviewed studies that utilized proteomics and metabolomics approaches to explore the multifaceted roles of CYPs in identifying disease markers and determining the contribution of CYP enzymes in developing treatment strategies. The applications of various cutting-edge analytical techniques, including liquid chromatography-mass spectrometry, nuclear magnetic resonance, and bioinformatics analyses in CYP proteomics and metabolomics studies, have been highlighted. The identification of CYP enzymes through metabolomics and/or proteomics in various disease conditions provides key information in the diagnostic and therapeutic landscape. Leveraging both proteomics and metabolomics presents a powerful approach for an exhaustive exploration of the multifaceted roles played by CYP enzymes in personalized medicine. Proteomics and metabolomics have enabled researchers to unravel the complex connection between CYP enzymes and metabolic markers associated with specific diseases. As technology and methodologies evolve, an integrated approach promises to further elucidate the role of CYPs in human health and disease, potentially ushering in a new era of personalized medicine.