Metastasectomy—the complete surgical resection of metastatic lesions—is increasingly performed despite advancements in systemic therapies. Spinal metastasectomy (SM) is particularly indicated for destructive osteolytic lesions that are prone to skeletal-related events and resistant to conventional systemic or radiation treatments. From this perspective, isolated lesions from kidney and thyroid cancers, and low-grade sarcomas are the best indication for SM. This study evaluated postoperative survival and prognostic factors in patients undergoing SM for isolated spinal metastases from renal cell carcinoma (RCC), differentiated thyroid carcinoma (DTC), and leiomyosarcoma (LMS). We retrospectively reviewed 65 patients with RCC, 22 with DTC, and 10 with LMS who underwent SM at our institution with a minimum 3-year follow-up. Cancer-specific survival (CSS) from the date of SM to death or last follow-up was estimated using Kaplan-Meier analysis. Factors associated with survival were identified using log-rank tests and Cox proportional hazard models. Local tumor recurrence within 3 years of SM occurred in 4 (6.2%), 3 (13.6%), and 2 (20.0%) patients with RCC, DTC, and LMS, respectively. Notably, no local recurrences were detected beyond 3 years postoperatively. The 3- and 5-year CSS rates were 77% and 62% for RCC, 91% and 77% for DTC, and 70% and 47% for LMS. Across all groups, poor postoperative functional status (ECOG Performance Status grade 3) was a significant common factor associated with shortened survival. SM for isolated, resectable spinal lesions from RCC, DTC, and LMS offers favorable oncological outcomes and survival benefits. Optimizing management depends on appropriate patient selection and timing of surgery, and the avoidance of major complications to preserve postoperative performance status.