 Abstract cancer cell extravasation, which involves arresting on the endothelium migrating through it and then invading the sub endothelial extracellular matrix of distant tissues, is a crucial step in the metastatic cascade. Research has mainly focused on the biomechanical interactions between tumor cells and the extracellular matrix at the primary tumor site, but very little is known about the mechanical properties of endothelial cells and the sub endothelial extracellular matrix and their role in the extravasation process. This paper develops an integrated experimental and theoretical framework to investigate the mechanical crosstalk between tumor cells, endothelium, and the sub endothelial extracellular matrix during in vitro cancer cell extravasation. The study finds that tumor cell actin-rich protrusions generate complex push-pull forces to initiate and drive extravasation, while transmigration success also depends on the forces generated by the endothelium. Furthermore, the mechanical properties of the sub endothelial extracellular matrix and endothelial actimiasin contractility that mediate the endofel. This article was authored by Yousef Javan-Marty, Ayushi Agrawal, Andrea Milandrano, and others. We are article.tv, links in the description below.