Advances in stereotactic radiosurgery (SRS), minimally invasive surgical techniques, and multidisciplinary care have transformed the outcomes of patients living with spine metastases. The incorporation of genomic biomarkers into management will likely enhance the ability to personalize treatment approaches. Within the field of oncology, genomic biomarkers have mainly been used for risk stratification and to inform the choice of systemic therapy. This has had a profound impact on the field of spine metastases, as patients are living longer with their metastatic disease, thus necessitating more durable yet less invasive treatment approaches. Recent evidence suggests that genomic biomarkers can also be used to guide the use of local therapy, such as radiotherapy dosing. Here, we review the current use of genomic biomarkers in the field of spine metastases. We also discuss emerging liquid biopsy technologies with a specific focus on potential applications of circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA). The overall goals for the use of genomic biomarkers in the field of spine oncology are to estimate overall prognosis, select combined modality approaches, guide radiotherapy dosing, enhance monitoring of therapeutic response, and detect treatment-related toxicity early.