Metastasis is a complex process that involved in various genetic and epigenetic alterations during the progression of breast cancer. Recent evidences have indicated that the mutation in the genome sequence may not be the key factor for increasing metastatic potential. Epigenetic changes were revealed to be important for metastatic phenotypes transition with the development in understanding the epigenetic basis of breast cancer. Herein, we aim to present the potential epigenetic drivers that induce dysregulation of genes related to breast tumor growth and metastasis, with a particular focus on histone modification including histone acetylation and methylation. The pervasive role of major histone modification enzymes in cancer metastasis such as histone acetyltransferases (HAT), histone deacetylases (HDACs), DNA methyltransferases (DNMTs), and so on are demonstrated and further discussed. In addition, we summarize the recent advances of next-generation sequencing technologies and microfluidic-based devices for enhancing the study of epigenomic landscapes of breast cancer. This feature also introduces several important biotechnologists for identifying robust epigenetic biomarkers and enabling the translation of epigenetic analyses to the clinic. In summary, a comprehensive understanding of epigenetic determinants in metastasis will offer new insights of breast cancer progression and can be achieved in the near future with the development of innovative epigenomic mapping tools.