Background and Objectives: Persistent sciatic artery (PSA) is a rare congenital vascular anomaly that is often asymptomatic, but can be associated with aneurysm formation and potential complications, such as thromboembolism or aneurysm rupture in some cases. We present a case of a 75-year-old woman with a symptomatic thrombus-containing aneurysm of the left PSA. Materials and Methods: The treatment of the PSA aneurysm involved a successful hybrid approach, which included open surgical bypass and endovascular embolization. The open surgical bypass was performed from the left common femoral artery to the left above-the-knee popliteal artery using a synthetic graft, while the aneurysm exclusion was achieved through endovascular plug embolization. Results: Control angiography revealed complete exclusion of the PSA aneurysm. At the 1-month follow-up, there were no palpable pulsatile masses in the left gluteal region, and the patient reported no symptoms. Conclusions: Given the high incidence of limb- and life-threatening complications associated with a PSA aneurysm, accurate diagnosis and appropriate treatment are crucial. In this case, a combination of open surgical and endovascular techniques resulted in a favorable outcome for the patient, highlighting the effectiveness of the hybrid approach in managing PSA aneurysms. Further studies are warranted to explore and refine treatment strategies for these complex vascular anomalies.