Patients with advanced stage completely resected endometrial cancer represent a heterogeneous group and decision-making regarding adjuvant treatment for this patient population is complex. When considering this cohort of patients, factors such as histologic subtype and molecular classification impact decision-making on adjuvant therapy. Options include systemic chemotherapy with or without immunotherapy or HER2-targeted therapy, chemoradiotherapy and radiation alone. We recommend tailoring treatment for patients with advanced-stage, non-measurable endometrial cancer based on HER2 status, mismatch repair (MMR) proficiency, disease stage and histology. For HER2-positive cases, we recommend carboplatin, paclitaxel, and trastuzumab. For HER2-negative, MMR-proficient disease, Stage 3 patients we recommend that have stage IIIB or IIIC disease AND grade 1 or 2 endometrioid histology OR grade 3 endometrioid histology p53 wild-type, we recommend carboplatin and paclitaxel, with consideration of the addition of pelvic radiationFor patients with stage IIIA disease OR grade 3 p53 aberrant endometrioid OR non-endometrioid histology, we recommend carboplatin and paclitaxel, with consideration of brachytherapy for patients with uterine risk factors such as lymphovascular space invasion, cervical stromal involvement, or lower uterine segment involvement. For Stage 4 patients with Her2 negative, MMRp disease, we recommend carboplatin and paclitaxel, with optional brachytherapy. For HER2-negative, MMR-deficient disease, the recommended regimen includes carboplatin, paclitaxel, and immunotherapy, with consideration of brachytherapy for patients with the uterine risk factors listed above.