Aim: The aim of this study is to predict the response of neoadjuvant chemotherapy (NACT) based on preoperative molecular subtyping of locally advanced breast cancer patients. Materials and Methods: The present single-blind, observational study was conducted at the tertiary health-care center of Acharya Vinoba Bhave Rural Hospital from October 2018 to September 2020. This study comprised 46 patients suffering from breast cancer with TNM stage IIIA and IIIB. The patients received either NACT with cyclophosphamide/adriamycin/5-fluorouracil or paclitaxel, respectively, followed by the standard surgical procedure of modified radical mastectomy. Baseline ultrasound was followed by Trucut biopsy of the tumor which was done with 18-G Bard Trucut biopsy needle under local anesthesia in all aseptic conditions. The specimens were collected and preserved in formalin and were sent for the assessment of tumor histological examination, Scarff-Bloom-Richardson grade, and immunohistochemistry (IHC) evaluation. Depending on the luminal status obtained by IHC preoperatively, further response to chemotherapy was assessed. Results: In the CAF group, patients with human epidermal growth factor receptor 2/neu (HER2/neu)-enriched status had (91.40% ± 7.76%) tumor response followed by luminal B status (89.33% ± 5.77%), triple-negative status (87.34% ± 9.55%), and finally luminal A status with (84.87% ± 8.11%) a statistically nonsignificant relation. In the paclitaxel group, patients with triple-negative status had a tumor response of (96.59% ± 4.48%) followed by luminal B status (96.28% ± 3.27%), HER2/neu-enriched status (91.33% ± 6.85%), and finally luminal A status (82.40% ± 11.29%) with a statistically significant relation (P = 0.023). Conclusion: It can be concluded from the results that overall, HER2/neu-enriched and triple-negative status patients showed better tumor response to NACT in both groups.