Cancer cells migrate through tight spaces, causing nuclear envelope (NE) rupture and DNA damage. This study investigates how tumor cells navigate confined environments, revealing that NE rupture occurs when the nucleus deforms to pass through narrow pores. NE rupture leads to chromatin protrusion, DNA damage, and nuclear fragmentation. Cells repair NE integrity using components of the ESCRT-III machinery, which is crucial for restoring nuclear membrane integrity and DNA damage repair. The study shows that NE rupture is more frequent in cells with reduced nuclear lamins and in confined environments. NE rupture is associated with increased DNA damage and genomic instability, which can lead to cell death if not repaired. The findings suggest that efficient NE and DNA repair mechanisms are essential for cancer cell survival during migration. The study also highlights the role of cytoskeletal forces and membrane curvature in NE rupture and repair. The results indicate that targeting NE repair and DNA damage repair pathways could be a strategy for developing anti-metastatic therapies.Cancer cells migrate through tight spaces, causing nuclear envelope (NE) rupture and DNA damage. This study investigates how tumor cells navigate confined environments, revealing that NE rupture occurs when the nucleus deforms to pass through narrow pores. NE rupture leads to chromatin protrusion, DNA damage, and nuclear fragmentation. Cells repair NE integrity using components of the ESCRT-III machinery, which is crucial for restoring nuclear membrane integrity and DNA damage repair. The study shows that NE rupture is more frequent in cells with reduced nuclear lamins and in confined environments. NE rupture is associated with increased DNA damage and genomic instability, which can lead to cell death if not repaired. The findings suggest that efficient NE and DNA repair mechanisms are essential for cancer cell survival during migration. The study also highlights the role of cytoskeletal forces and membrane curvature in NE rupture and repair. The results indicate that targeting NE repair and DNA damage repair pathways could be a strategy for developing anti-metastatic therapies.