Introduction  Breast cancer is a major cause of mortality among females, worldwide. The present study was intended to evaluate the significance in the management of carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) in patients with breast cancer. Methodology A cohort study was conducted at the Jinnah Postgraduate Medical Center, Karachi, Pakistan from June 2020 to May 2021. All diagnosed cases of breast cancer who underwent surgical excision of tumor were eligible to partake. Patients who had metastatic breast cancer or had a recurrence were excluded. The patient's sociodemographic and clinical data were documented in a predefined pro forma. It included information about the age, sex, weight, as well as serum CEA and CA15-3. The CA15-3 and CEA levels for each patient were assessed by taking a 5ml blood sample and sending it to the laboratory for further workup. preoperatively on the second, seventh, and 28th postoperative days. Results A mean ± SD age of 52.6 ± 8.89 years was reported. Family history of breast cancer was positive in one-fourth of the patients. Nodal metastasis was negative in 114 (46.72%) patients. Three-fourth of patients had Stage II-IV with only a minority diagnosed with Stage I. The mean levels for CA15-3 in women with Stage I cancer was significantly lower on the seventh day and 28th postoperative day, compared to preoperative levels (p = 0.05). Similar associations were seen for stages II and III. Higher CEA levels were significantly associated with stage III breast cancer preoperatively (5.88 ng/ml, p = 0.05) compared to postoperative values. Conclusion The current study revealed that preoperative values of serum CEA and CA15-3 significantly reduced postoperatively. Moreover, patients with advanced cancers had significantly higher levels of both tumor markers than those with less advanced diseases. The current study highlighted the importance of regular assessment of serum CEA and CA15-3 in breast cancer patients. Both these biomarkers are substantially elevated in breast cancer patients, preoperatively. Determining the levels of serum CEA and CA15-3 pre- and postoperatively may determine the prognosis and aid in forming the most optimal patient care regime with respect to the stage and subtype of cancer.