<p>Tumor metastasis involves the spread of tumor cells from the primary site to distant organs via the lymphatic system, blood vessels, and other pathways. It stands as a major contributor to cancer incidence and mortality. Laminin α5 (LMα5) is a member of the laminin family, which is widely expressed in various tumor tissues and is significantly associated with poor cancer prognosis. Laminin α5 plays an important role in cancer metastasis, serving as a key regulator in this process. LMα5 facilitates tumor metastasis through its interactions with various receptors, including integrins and Lutheran/basal cell adhesion molecules (Lu/BCAM). Moreover, it modulates the epithelial–mesenchymal transition (EMT) by influencing the Notch signaling pathway, thus regulating the invasive capabilities of tumor cells. By mediating the interplay between tumors and their microenvironment, LMα5 disrupts the adhesion of tumor cells to vascular endothelial cells, consequently reducing metastatic tumor growth. In this review, we have discussed the core mechanisms of action underlying the role of LMα5 in tumor metastasis and its therapeutic potential. By shedding light on novel therapeutic targets and treatment strategies, the aim is to combat cancer metastasis and improve the efficacy of cancer treatments.</p>