Epiretinal membrane is a type of fibrous proliferation on the retinal surface in the macular region. Its most common symptoms include metamorphopsia, micropsia, macropsia, and reduced visual acuity. When these symptoms are present, patients are typically treated surgically with posterior vitrectomy. During the procedure, both the epiretinal membrane and the internal limiting membrane are removed. Postoperatively, an improvement in visual acuity and resolution of membrane-related symptoms are generally observed. A particular clinical challenge arises when epiretinal membrane coexists with diabetic macular edema or exudative age-related macular degeneration. In such cases, the membrane is believed to reduce the effectiveness of anti-vascular endothelial growth factor therapy. When these conditions coexist, surgical treatment may also be applied; however, outcomes are not always satisfactory. It is generally assumed that surgery should be performed at least after a loading phase of pharmacological therapy and, optimally, after a longer period if therapeutic effects remain insufficient. This paper reviews the available literature and presents clinical cases of patients treated with both surgical intervention and anti-vascular endothelial growth factor therapy.