The retinal pigment epithelium (RPE), as a single layer of cells that performs multiple functions posteriorly in the eye, is a promising target site for the prevention and treatment of several clinical diseases, including proliferative diabetic retinopathy, age-related macular degeneration, chorionic neovascularization, and retinitis pigmentosa. In recent decades, several nanodrug delivery platforms and tissue-engineered RPE have been widely developed to treat RPE-related diseases. This work summarizes the recent advances in nanoplatforms and tissue engineering scaffolds developed in these fields. The diseases associated with pathological RPE and their common therapy strategies are first introduced. Then, the recent progress made with a variety of drug delivery systems is presented, with an emphasis on the modification strategies of nanomaterials for targeted delivery. Tissue engineering-mediated RPE transplantation for treating these diseases is subsequently described. Finally, the clinical translation challenges in these fields are discussed in depth. This article will offer readers a better understanding of emerging nanotechnology and tissue engineering related to the treatment of RPE-related diseases and could facilitate their widespread use in experiments in vivo and in clinical applications.