Objective: To explore the clinical efficacy and safety of percutaneous minimally invasive partial resection of vertebral lesions combined with decompression and percutaneous vertebroplasty (PVP) in the treatment of thoracolumbar metastatic tumors. Methods: The clinical data of 54 patients with thoracolumbar metastatic tumors who underwent percutaneous minimally invasive partial resection of vertebral lesions combined with decompression and PVP injection in our hospital from January 2020 to June 2024 were analyzed retrospectively. All patients received local anesthesia. There were 27 males and 27 females, including 31 cases of thoracic vertebral metastases, 18 cases of lumbar vertebral metastases, and 5 cases of thoracolumbar vertebral metastases. The Visual Analog Scale (VAS) score for pain and Oswestry Disability Index (ODI) before surgery and 1 week after surgery were compared. Meanwhile, the operation time, intraoperative blood loss, bone cement leakage, and other complications were recorded. Results: All patients successfully completed the operation. The operation time was 45–90 (67.89 ± 11.96) minutes, and the intraoperative blood loss was 30–100 (60.19 ± 20.16) mL. All patients were followed up for 3–12 months, with an average of 7.8 months. Except for 5 patients who experienced bone cement leakage, all other patients had their lesions healed smoothly, with no intraspinal leakage or other complications. The preoperative VAS score was 6–9 (7.69 ± 1.03) points, and the ODI was 51–79% (74.70 ± 7.64)%. One week after surgery, the VAS score was 1–3 (2.07 ± 0.70) points, which was significantly improved compared with that before surgery (P < 0.05). One week after surgery, the ODI was 24–41% (31.93 ± 4.43)%, which was also significantly improved compared with that before surgery (P < 0.05). Conclusion: Percutaneous minimally invasive partial resection of vertebral lesions combined with decompression and PVP injection in the treatment of thoracolumbar metastatic tumors has the advantages of minimal invasiveness, effective relief of cancer-related pain, restoration of vertebral stability, and few complications, which is conducive to improving the quality of life of patients.