The metastatic process in breast cancer is complex and with different inherent mechanisms depending on the cancer subtype. Subtype switching from less aggressive to more aggressive subtypes is a well-known phenomenon; however, the molecular alterations acquired through this process remain poorly understood. In this study, we profiled a series of 55 paired primary and metastatic samples with detailed clinical coordinates to uncover key molecular alterations important in the metastatic process. Multi-platform sequencing further describes varying molecular features which contribute to the metastatic evolutionary process. Harnessing spatial transcriptomics, we describe the intra-tumoral heterogeneity in matched primary and metastatic pairs. Finally, integrating detailed clinical data demonstrates the impact of treatment decisions in metastatic breast cancer. This study improves our understanding of the metastatic process. Ultimately, we hope further analyses will continue to uncover novel understanding for both prevention and treatment of metastatic cancer.