Worldwide, the incidence of endometrial cancer is increasing. Although the prognosis remains good for patients diagnosed with early-stage disease, for those diagnosed with recurrent or metastatic disease, options have been limited, and prognosis is short. Optimizing and identifying new well-tolerated treatments for women living with endometrial cancer is a top priority. A new era is dawning where we are starting to see the integration of clinically relevant genomic and pathologic data to inform and refine treatment strategies for women with endometrial cancer. Here, we focus on reviewing nonimmunotherapy-based targeted treatment options and emerging directions for women with endometrial cancer.