Breast cancer (BC) is the second leading cause of cancer-related death in American women and more than 90% of BC-related death is caused by metastatic BC (MBC). This review stresses the limited success of traditional therapies as well as the use of nanomedicine for treating MBC. Understanding the biological barriers of MBC that nanoparticle in vivo trafficking must overcome could provide valuable new insights for translating nanomedicine from the bench side to the bedside. A view about nanomedicine applied in BC therapy has been summarized with their present status, which is gaining attention in the clinically-applied landscape. The progressions of drug/gene delivery systems, especially the status of their preclinical or clinical trials, are also discussed. Here we highlight that the treatment of metastasis, in addition to the extensively described inhibition of primary tumor growth, is an indispensable requirement for nanomedicine. Along with more innovations in material chemistry and more progressions in biology, nanomedicine will constantly supply more exciting new approaches for targeted drug/gene delivery against MBC.