We present a case of combined surgical screw placement and osteoplasty guided by computed tomography-fluoroscopy (CTF) in a 68-year-old man with unilateral osteolytic destruction and a pathological fracture of the iliosacral joint due to a metastasis from renal cell carcinoma. The patient experienced intractable lower back pain that was refractory to analgesia. After transarterial particle and coil embolization of the tumor-feeding vessels in the angiography unit, the procedure was performed under general anesthesia by an interdisciplinary team of interventional radiologists and trauma surgeons. Under intermittent single-shot CTF, two K wires were inserted into the left iliosacral joint from a lateral transiliac approach at the S1 level followed by two self-tapping surgical screws. Continuous CTF was used for monitoring of the subsequent polymethylmethacrylate injection through two vertebroplasty cannulas for further stabilization of the screw threads within the osteolytic sacral ala. Both the screw placement and cement injection were successful, with no complications occurring during or after the procedure. With additional nonsteroidal anti-inflammatory and opioid medication, the patient reported a marked decrease in his lower back pain and was able to move independently again at the 3-month follow-up assessment. In our patient with intolerable back pain due to tumor destruction and consequent pathological fracture of the iliosacral joint, CTF-guided iliosacral screw placement combined with osteoplasty was successful with respect to joint stabilization and a reduction in the need for analgesic therapy.