• Cell adhesion molecules (CAMs) orchestrate monocyte transendothelial migration and macrophage polarization in a spatiotemporal manner.
• CAMs activate NF-κB and STAT signaling pathways to dictate macrophage plasticity in inflammation and tumor microenvironments.
• Dual roles of CAMs in atherosclerosis and cancer highlight their potential as therapeutic targets.
• CAM-based bioengineering offers promising strategies for regenerative medicine and targeted immunotherapies.