Purpose: To identify patients with complete pathological response (ypT0N0) after neoadjuvant treatment and total mesorectal excision (TME) for rectal cancer, and evaluate clinical decision-making and surgical outcomes in these cases. Methodology: This single-institution cohort study analyzed patients undergoing neoadjuvant treatment for rectal cancer from January 2016 to December 2024. Data were collected from a prospectively maintained oncology database. Clinical decisions were retrieved from multidisciplinary team discussions. MRI images and pathological specimens for ypT0N0 cases were reviewed. Results: Of 109 patients treated with neoadjuvant therapy, 68 underwent TME resection. Neoadjuvant approaches evolved from long-course chemoradiation followed by routine TME to total neoadjuvant therapy followed by TME resection or watch-and-wait strategy. Twelve patients (18%) were identified with ypT0N0 pathology. Factors contributing to the decision to resect included persistent tumor signal on MRI (6/12 patients), endoscopic evaluation (3/12 patients), and digital rectal examination (3/12 patients). Patients underwent either abdominoperineal resection or ultra-low anterior resection, with 6/12 patients experiencing Clavien-Dindo grade 3 or 4 complications. Conclusions: Improving accuracy in determining complete pathological response to neoadjuvant therapy is crucial to prevent unnecessary surgery. This study suggests that current clinical investigations may lead to overtreatment in some cases. Incorporating additional definitive methods, such as ultrasound-guided biopsy or transanal minimally invasive surgery (TAMIS) for tissue sampling, may enhance the accuracy of confirming malignancy persistence or recurrence.