Metaplastic breast cancer (MBC) constitutes a rare clinical entity with special clinicopathologic, immunohistochemical, and molecular features. Resistance to systemic therapies, whether chemotherapy or hormonal therapy, is among its main characteristics, which in turn explains the poor prognosis and renders its management a challenge. Thus, the scope of the present review is to discuss the current therapeutic strategies for MBC in clinical practice and the corresponding outcomes and to suggest possible directions for future research. Potential novel targeted therapies could provide a hope for better outcomes but limited data are available owing to the rarity of MBC. As knowledge accumulates on the pathogenesis and genetic characteristics of MBC, emphasis should be given to the implementation of more targeted treatments, which will allow more efficient and individualized management of the disease.