Cancer metastasis is still a major social issue with limited knowledge of the formation of tumors and their growth. In addition the formation of metastases is very difficult to understand, since it involves very complex physical mechanisms such as cellular interactions and cell rheology, which are flow-dependent. Previous studies investigated transendothelial migration using sophisticated techniques such as microfluidics, traction force microscopy (TFM) or Atomic Force Microscopy (AFM), combined with physical modeling. Here we summarize recent results and suggest new ways to investigate the precise mechanisms used by cancer cells to undergo transendothelial migration.