Many tumors prefer to metastasize to bone, but the underlying mechanisms remain elusive. The human skeletal system has unique physical properties, that are distinct from other organs, which play a key role in directing the behavior of tumor cells within bone. Understanding the physical journey of tumor cells within bone is crucial. In this review we discuss bone metastasis in the context of how physical cues in the bone vasculature and bone marrow niche regulate the fate of tumor cells. Our objective is to inspire innovative diagnostic and therapeutic approaches for bone metastasis from a mechanobiological perspective.