In neuroblastoma, p53 and TAp73 act as safeguards against malignant transformation, but they are commonly inhibited by negative regulators, such as MDMs, Itch, and Aurora kinase A. This review focuses on the relevant tumor suppressor role of p53 and TAp73 in neuroblastoma, further addressing their connection with crucial biomarkers of poor prognosis, such as N-MYC, and their great potential as therapeutic targets. The gene discussed is MYCN; the disease is neuroblastoma.