Although not considered curative in nature, new therapeutic advances in metastatic breast cancer (MBC) have substantially improved patient outcomes. This article discusses the state-of-the-art and emerging therapeutic options for management of MBC. BC systemic therapy targets multiple key pathways, including estrogen receptor signaling, HER2 signaling, and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling. Other therapeutic strategies include targeting DNA repair, inhibiting immune checkpoints, and developing antibody-drug conjugates. Although surgery historically was reserved for palliation of symptomatic, large, or ulcerating masses, some data suggest a possibly expanding role for more aggressive locoregional therapy in combination with systemic therapy. As technology develops, biomarker-specific, line-agnostic, and receptor-agnostic treatment strategies will redraw the current lines of MBC care. However, tumor heterogeneity remains a challenge. To effectively reshape our approach to MBC, careful consideration of the patient perspective, the costs and value of novel treatments, and accessibility (especially in developing countries) is paramount.