Breast cancer (BrCa) mortality results predominately from distant metastases. In some instances, these disseminated cells remain dormant for long periods of time. The metastatic microenvironment seemingly protects micrometastases providing resistance to agents that eradicate the primary mass. The lack of relevant accessible model systems for micrometastases has hindered the development of effective therapies. To address this gap, we developed an innovative all-human 3D ex vivo hepatic microphysiological system (MPS) to reproduce human physiology and thereby facilitate the investigation of BrCa behavior in a micrometastatic niche. The liver is a major site of metastasis for carcinomas and the primary site of drug metabolism, a significant factor in determining efficacy and limiting toxicities of cancer therapies. The system is established with fresh human hepatocytes and non-parenchymal cells, creating a microenvironment into which BrCa cells (MDA-MB-231) are seeded. The MPS maintains physiologic function of the hepatic niche through 15d and BrCa cells effectively integrate into the hepatic tissue. Spontaneous growth attenuation is observed amongst a subpopulation of BrCa cells (Ki67-/EdU-) after 12d in culture. Further, we demonstrate that the cycling BrCa cells are eradicated by chemotherapy (doxorubicin), while those that survive are non-proliferating (Ki67-/EdU-). Notably, the later persisting chemoresistant dormant BrCa cell population can be stimulated to re-emerge and proliferate in the presence of stress stimuli, mimicking the dormancy and outgrowth observed in patients. Analyses of the milieu effluent also identified signaling molecules from non-parenchymal cells that may influence the metastatic cell fraction entering dormancy. This MPS provides unprecedented insights into the tumor biology of dormant micrometastases. Ultimately, it provides an accessible tool to identify new therapeutic strategies for metastasis during initial seeding, dormancy and re-emergence, while concurrently evaluating agent efficacy for metastasis, metabolism and dose-limiting toxicity.