We present a case of Cesarean scar ectopic pregnancy, complicated by the persistence of clinical symptoms despite a rapid and complete biochemical response to a single systemic injection of methotrexate. A 34-year-old woman with three previous Cesarean sections was diagnosed with a Cesarean scar ectopic pregnancy following in-vitro fertilization treatment. The diagnosis was suggested by three-dimensional (3D) ultrasound scan and confirmed with magnetic resonance imaging (MRI). Management involved administration of a single systemic injection of methotrexate and follow-up with serial ultrasound assessments and serum beta-human chorionic gonadotropin (beta-hCG) measurements. The main challenge was the persistence of clinical symptoms despite adequate medical treatment, as judged by complete resolution of biochemical trophoblastic activity, which resulted in repeated admissions to the hospital. Serial transvaginal ultrasound scans showed an initial increase in the size of the mass, which led to increasing anxiety in the couple. Eventually, 15 weeks after the administration of methotrexate, the couple requested surgical intervention. An uneventful surgical resection of the abnormal area, which showed appearances suggestive of trophoblastic tissue, was undertaken to good effect. In summary, despite a rapid normalization of serum beta-hCG following the administration of methotrexate, the patient remained symptomatic and had ultrasound appearances suggestive of incomplete resorption of trophoblast, necessitating surgical intervention.