Purpose <p>Accurate assessment of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) remains challenging in breast cancer. This prospective single-center study compared [⁶⁸Ga]Ga-FAPI-04 PET/MRI, [¹⁸F]FDG PET/CT, and contrast-enhanced MRI for predicting pathologic response after NAC.</p> Methods <p>Women with biopsy-confirmed stage II–III breast cancer underwent baseline and post-therapy [⁶⁸Ga]Ga-FAPI-04 PET/MRI, [¹⁸F]FDG PET/CT, and contrast-enhanced MRI before surgery. PET parameters were analyzed for primary tumors and axillary nodes. Selected variables were evaluated using LASSO and receiver-operating-characteristic analyses. Stromal FAP expression was assessed immunohistochemically in paired specimens.</p> Results <p>Twenty-four patients completed the protocol, yielding 25 primary lesions and 44 metastatic lymph nodes across 27 axillary compartments. The pCR rate was 60.00% for primary lesions and 72.73% for axillary nodes. For primary-lesion response, post-therapy [⁶⁸Ga]Ga-FAPI-04 SUVmax showed the highest performance (AUC, 0.84; sensitivity, specificity, and accuracy, 80.00% each); the best [¹⁸F]FDG parameter was ΔTBR% (AUC, 0.747). For nodal response, post-therapy [⁶⁸Ga]Ga-FAPI-04 SULmean showed the highest performance (AUC, 0.89; sensitivity, 91.67%; specificity, 81.25%; accuracy, 84.09%) and exceeded the best [¹⁸F]FDG parameter on DeLong testing. MRI AUCs were 0.733 and 0.770 for primary and nodal disease, respectively. Stromal FAP expression correlated positively with [⁶⁸Ga]Ga-FAPI-04 SUVmax.</p> Conclusion <p>Post-therapy [⁶⁸Ga]Ga-FAPI-04 PET may provide useful adjunctive information for response assessment after NAC in breast cancer, particularly for axillary nodal evaluation, potentially supporting more individualized preoperative planning.</p> Trial registration <p>ClinicalTrials.gov, NCT07553741, retrospectively registered.</p>