Objectives: This study aims to identify clinical characteristics and biomarkers influencing survival outcomes in colorectal cancer (CRC) patients with spinal metastases. Methods: We conducted a retrospective cohort study involving 27 patients treated for CRC-derived spinal metastases at Johns Hopkins Hospital. Data on demographics, biomarker profiles of the primary colorectal tumor site, surgical outcomes, and survival were collected. Neurological function was assessed pre- and postoperatively using Frankel scores. Survival outcomes included overall survival (OS) and post-metastasis survival. Results: The median age of the patients was 58 years, with 63% being women. The sacral spine was the most frequently involved site (59.3%), followed by the thoracic and lumbar regions. Most patients (89%) already had extraspinal metastases, predominantly in the lungs. Biomarker analysis showed microsatellite stability in 63% of patients and CDX2 (Caudal-type homeobox 2) expression in 37%. Laminectomy was performed in 85% of cases and sacrectomy in 55.6%, leading to postoperative improvements in ambulatory function and neurological status. The main indications included local recurrence of the tumor and neurological deficits attributed to the impinging tumor. The median overall survival was 4.9 years, while the median post-metastasis survival was 3.0 years. Univariable analysis revealed that CK20 expression (p = 0.041) and spinal tumor recurrence (p = 0.045) were significantly associated with shorter post-metastasis survival. Conclusions: This study highlights the prognostic importance of CK20 expression and spinal tumor recurrence in CRC patients diagnosed with spinal metastases. Surgical intervention significantly improved neurological outcomes, enhancing patient quality of life. Further research with larger cohorts is needed to confirm these findings and optimize treatment strategies for this challenging patient population.