Diabetic macular edema (DME) is the most threatening complication of diabetic retinopathy that affects visual function, which is characterized by intractability and recurrent attacks. Currently, the clinical routine treatments for DME mainly include intravitreal injection, grid laser photocoagulation in the macular area, subthreshold micropulse laser, periocular corticosteroid injection, and vitrectomy. Although conventional treatments are effective for some patients, persistent, refractory, and recurrent DME remains a clinical challenge that needs to be urgently addressed. In recent years, clinical studies have found that certain combination therapies are superior to monotherapy, which can not only restore the anatomical structure of the macular area and effectively reduce macular edema but also improve visual function to some extent while reducing the number of treatments and the overall cost. This makes up for the shortcomings of single treatment modalities and is highly anticipated in the clinical setting. However, the application of combination therapy in clinical practice is relatively short, and its safety and long-term effectiveness need further exploration. Currently, new drugs, new formulations, and new therapeutic targets are still under research and development to address different mechanisms of DME occurrence and development, such as anti-vascular endothelial growth factor agents designed to anchor repetitive sequence proteins with stronger inhibition of vascular leakage, multiple growth factor inhibitors, anti-inflammatory agents, and stem cell therapy. With the continuous improvement of the combination application of existing drugs and treatments and the development of new drugs and treatment technologies, personalized treatment for DME will become possible.