Evidence from studies in pediatric patients regarding the EPH/ephrin system’s involvement in these types of neoplasms is limited, and we aimed to shed light on the currently available evidence as an impetus for further investigation, especially regarding targeting EPHA2 with Dasatinib, Pazopanib, and Trametinib, which have been already used off-label in pediatric solid tumors with promising results [72,74,75,76,77,78,79,80,116,117,118,119,120]. The gene discussed is EPHA2; the disease is neoplasm.