He ran for mayor of Agrigento at the 2007 Italian local elections, supported by a coalition composed of the Union of the Centre (UdC), Democrats of the Left (DS), and UDEUR.
[2] In 2023, alongside Action politicians Carlo Calenda, Enrico Costa, and Mariastella Gelmini, Zambuto put forward a law proposal to decriminalize the abuse of office.
[8][9][10] On 31 March 2015, Zambuto resigned from the position of president of the Regional Assembly of the PD in Sicily following a controversy sparked by his visit to Silvio Berlusconi in Arcore.
[2] On 4 January 2021, he was appointed regional councilor for local authorities and public functions by the then Sicily president Nello Musumeci;[2] he held this position until 2022.
[13] For the 2024 European Parliament election in Italy, Zambuto is considered to be a candidate within Salvatore Cuffaro's Christian Democracy Sicily (DCS) as part of a deal between Renzi and Cuffaro,[12] who is Zambuto's brother-in-law,[7] for Renew Europe's United States of Europe list in Italy.