Diabetic macular edema (DME) is the primary cause of central vision impairment in patients with diabetes and the leading cause of preventable blindness in working-age people. With the advent of optical coherence tomography and antivascular endothelial growth factor (anti-VEGF) therapy, the diagnosis, evaluation, and treatment of DME were greatly revolutionized in the last decade. However, there is tremendous heterogeneity among DME patients, and 30%–50% of DME patients do not respond well to anti-VEGF agents. In addition, there is no evidence-based and universally accepted administration regimen. The identification of DME patients not responding to anti-VEGF agents and the determination of the optimal administration interval are the 2 major challenges of DME, which are difficult to achieve with the coarse granularity of conventional health care modality. Therefore, more and more retina specialists have pointed out the necessity of introducing precision medicine into the management of DME and have conducted related studies in recent years. One of the most frontier methods is the targeted extraction of individualized disease features from optical coherence tomography images based on artificial intelligence technology, which provides precise evaluation and risk classification of DME. This review aims to provide an overview of the progress of artificial intelligence-enabled precision medicine in automated screening, precise evaluation, prognosis prediction, and follow-up monitoring of DME. Further, the challenges ahead of real-world applications and the future development of precision medicine in DME will be discussed.