A lack of effective treatments for patients suffered from breast cancer with bone metastasis are caused by limited in vitro models and unsuitable animal models, which leads to 70%~80% mortality rate. Microfluidics enabled bone-on-a-chip could facilitate the resemblance of the biochemical and biophysical microenvironment of native bone tissues, which could readily be incorporated with the occurrence of breast cancer so as to recapture the bone metastasis in a single chip. The microscale chip design could be scaled up with high throughput/content settings so as to uncover the molecular mechanisms existing in bone metastasis of breast cancer and screen effective drugs for it more efficiently. In this review, we first introduce the current mechanistic understanding on bone metastasis of breast cancer and existing drugs for this disease. We then summarized the microfluidic models used for recapturing bone metastasis phenomena. We also presented high throughput designs aiming for more efficient drug discovery and development. Lastly, we discuss the advantages and challenges existing in combining high throughput setting and microfluidic models aiming for effective drug screening targeting bone metastasis of breast cancer. Together, we hope to provide a clue on how effective treatments could be discovered in the future so as to decrease the high mortality rate of bone metastasis of breast cancer.