Matrix metalloproteinases (MMPs) play critical roles in tumor metastasis by interacting with the tumor microenvironment and distant pre-metastatic sites. Their functions are regulated by spatial and temporal interactions with cellular and extracellular components. While MMPs are well-studied for their roles in tumor-induced angiogenesis, invasion, and metastatic focus establishment, their roles in other metastatic steps, such as tumor cell escape, intravasation, survival in circulation, and extravasation, remain underexplored. Molecular genetic studies using knock-out or transgenic animals and modified tumor cell lines have provided compelling evidence for the dual roles of MMPs in metastasis, showing both pro- and anti-metastatic effects depending on their nature and experimental context. Tumor metastasis is a multistep process involving tumor cell survival and communication skills, with each phase being a rate-limiting step. MMPs interact with the extracellular matrix, basement membranes, endothelial cells, and the secondary site microenvironment, and their expression is linked to cancer progression. Elevated MMP levels are associated with increased tumor invasion and metastasis, while some MMPs, like MMP-8 and MMP-3, show negative correlations with cancer progression. However, the relationship between MMP expression and prognosis is complex and varies among cancers. MMPs are also involved in angiogenesis, which is a critical target for MMP inhibitors. In vivo studies using transgenic mice and xenograft models have shown that both tumor-derived and host-derived MMPs contribute to metastasis. The expression of MMPs is often accompanied by increased TIMP levels, which can have conflicting effects on tumor progression. Overall, MMPs are essential for metastasis, but their roles are context-dependent, highlighting the need for further research to fully understand their functions in cancer progression.Matrix metalloproteinases (MMPs) play critical roles in tumor metastasis by interacting with the tumor microenvironment and distant pre-metastatic sites. Their functions are regulated by spatial and temporal interactions with cellular and extracellular components. While MMPs are well-studied for their roles in tumor-induced angiogenesis, invasion, and metastatic focus establishment, their roles in other metastatic steps, such as tumor cell escape, intravasation, survival in circulation, and extravasation, remain underexplored. Molecular genetic studies using knock-out or transgenic animals and modified tumor cell lines have provided compelling evidence for the dual roles of MMPs in metastasis, showing both pro- and anti-metastatic effects depending on their nature and experimental context. Tumor metastasis is a multistep process involving tumor cell survival and communication skills, with each phase being a rate-limiting step. MMPs interact with the extracellular matrix, basement membranes, endothelial cells, and the secondary site microenvironment, and their expression is linked to cancer progression. Elevated MMP levels are associated with increased tumor invasion and metastasis, while some MMPs, like MMP-8 and MMP-3, show negative correlations with cancer progression. However, the relationship between MMP expression and prognosis is complex and varies among cancers. MMPs are also involved in angiogenesis, which is a critical target for MMP inhibitors. In vivo studies using transgenic mice and xenograft models have shown that both tumor-derived and host-derived MMPs contribute to metastasis. The expression of MMPs is often accompanied by increased TIMP levels, which can have conflicting effects on tumor progression. Overall, MMPs are essential for metastasis, but their roles are context-dependent, highlighting the need for further research to fully understand their functions in cancer progression.