Cancer metastasis is still a major society issue with some limited knowledge of the formation of tumors and their growth. In addition the formation of metastases is still very difficult to understand, as tumor cells escape from an initial tumor, travel through the vasculature and finally escape through the vessel wall. This involves very complex physical mechanisms such as cellular interactions and cell rheology, which are flowdependent. The previous parameters have been recently investigated using sophisticated techniques such as flow chambers, microfluidics, traction force microscopy (TFM) or other mechanical tools such as optical manipulators or Atomic Force Microscopy (AFM), combined with physical modelling. Here we summarize recent results and raise the question of the best possible ways to investigate the precise mechanisms used by cancer cells to undergo transendothelial migration.