<p>Vascular cell adhesion molecule (VCAM)-1 has garnered significant research attention due to its potential as a disease biomarker and drug target across several inflammatory pathologies—including atherosclerosis, asthma, rheumatoid arthritis, and inflammatory bowel disease (IBD). The VCAM-1 protein has also been noted for its functional involvement in cancer metastasis and drug resistance to conventional chemotherapeutics. Although the anti-inflammatory and anti-cancer facets of VCAM-1 antagonisation have been examined separately, there is yet to be a review that explicitly addresses the functional interrelationship between these mechanisms. Furthermore, the pleiotropic mechanisms of anti-VCAM-1 therapies may present a useful paradigm for designing drug candidates with synergistic anti-inflammatory and anti-tumorigenic effects. The pathological overlap between inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CRC) serves as the quintessential disease model to observe this therapeutic duality. This review thereby details the adhesive mechanisms of VCAM-1 in colorectal disease—specifically, driving immune cell infiltration during IBD and tumour cell metastasis in CRC—and posits the potential of this receptor as a common drug target for both diseases. To explore this hypothesis, the current progress of novel VCAM-1-directed drug candidates in experimental models of IBD and CRC is also discussed.</p> Graphical Abstract <p><b>TOC Figure:</b> Graphical abstract illustrating the multi-functional role of vascular cell adhesion molecule (VCAM)-1 in colorectal diseases. VCAM-1 facilitates adhesive cell-to-cell attachments <i>via</i> a receptor-ligand binding mechanism with its complementary integrin ligands, α₄β₁ and α₄β₇. These VCAM-1-mediated interactions are involved in both inflammatory cell recruitment during inflammatory bowel disease (IBD) and cancer cell metastasis in colorectal cancer (CRC), highlighting the therapeutic potential of VCAM-1 as a drug target for both pathologies</p> <p></p>