Extracellular vesicles (EVs) are secreted in the extracellular space, can travel through the blood stream and are transferred to target (stromal) cells. This makes EVs an important means of cell-to-cell communication both at local and distant sites (metastasis). EVs can reprogram signalling pathways in stromal cells promoting the formation of a supportive tumour microenvironment (TME) and pre-metastatic sites/niches. The mechanisms that drive the formation of 'defined’ pre-metastatic sites and promote metastasis formation with associated cancer cells growth and drug resistance is still poorly understood in multiple myeloma (MM), an incurable blood cancer.