<p>Bone is the most common site of metastasis in patients with advanced breast cancer and serves as a reservoir from which secondary metastases often originate. While research has traditionally focused on understanding the biochemical signals involved in bone metastasis, bone matrix changes are inextricably linked with its pathogenesis as well. Indeed, decreased bone matrix density is both a symptom of late-stage disease and a risk factor for metastasis formation. Vice versa, raising bone density protects against metastasis. How bone matrix controls metastatic outgrowth and progression and which biochemical or biophysical mechanisms are involved in these processes is poorly understood due in part to limitations in current models of bone metastasis. In this review, we discuss the role of bone matrix in the microenvironmental regulation of bone metastasis and its effect on mechanosignaling and highlight current and future engineered model systems that have the potential to yield new mechanistic insights to advance the clinical prognosis of breast cancer patients.</p>