Retinoblastoma (RB) is a rare and deadly childhood ocular malignancy. In recent years, there has been a shift toward intra-arterial chemotherapy (IAC) as its primary treatment, providing an alternative to traditional enucleation, systemic chemotherapy, and external beam radiation. IAC directly administers chemotherapy drugs in the ophthalmic artery. This approach allows for targeted and higher dose delivery, improving tumor control, ocular survival, and the quality of patients’ lives. Technical advancements in microcatheter delivery systems and optimized drug selection have improved the success rates and safety of the procedure. While challenges and limitations exist in adopting IAC as the primary RB treatment, it significantly improves patient outcomes and reduces the need for enucleation. IAC-RB is an example of an effective endovascular treatment of neurological malignancy.