Rectal cancer is a leading cause of cancer death in the United States. Current standard of care in locally advanced rectal cancer includes chemoradiation therapy followed by surgical resection. Accurate radiological restaging therapy is essential for success of surgery. In this preliminary study, we investigated the synergistic role of rectal mpMRI and F18-FDG PET/MR in evaluation of response to therapy in advanced rectal cancer. Our data show promising added value of this “one-stop” imaging modality in providing complementary morphological and functional information in the detection of viable primary tumor as well as nodal and distal metastases, utilizing both MRI and PET molecular imaging biomarkers.