Colorectal cancer (CRC) is a complex disease influenced by various genetic, epigenetic, and environmental factors. The integration of multi-omics approaches, which include genomics, transcriptomics, proteomics, and metabolomics, has significantly advanced our understanding of CRC development, progression, and the molecular landscape of CRC tumors, leading to the identification of potential biomarkers and therapeutic targets. One of the key areas of interest in CRC research is the role of the gut microbiome in modulating tumor development, maintaining gut homeostasis, immune function, and response to treatment. An imbalance in the gut microbiome has been linked to various diseases, including CRC, and modulating the gut microbiome could be used as a novel therapeutic approach for CRC. By targeting specific microbes or microbial pathways, researchers aim to enhance the antitumor immune response and inhibit tumor growth. By integrating data, researchers can identify microbial signatures associated with CRC development and progression. These signatures may serve as biomarkers for early detection or prognosis, as well as potential targets for therapy. This chapter illuminates the basic concepts pertaining to CRC with a focus on elaborating various multi-omics approaches that are instrumental in elucidating the complex interactions between the gut microbiome and CRC.