The Old Lady have chosen former Italy manager the veteran manager to take the helm for the rest of the term.
Spalletti replaces his predecessor, who was sacked after the Serie A side's defeat by Lazio last weekend.
Tudor arrived at the club in March as Thiago Motta's replacement but exited following a seven-month stint after an eight-game winless streak.
Spalletti guided Napoli to the Serie A crown in 2022-23 prior to assuming the Italy role, which missed out on the 2022 World Cup with Mancini at the helm.
He helped them qualify for Euro 2024 but were eliminated in the round of 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti in June after a World Cup qualifying defeat by Norway, putting Italy in danger of missing a third straight World Cup.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and secured two Russian Premier League titles with Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus for their 3-1 win against Udinese on Wednesday moving them to seventh position in the league - six points adrift of Napoli at the top after nine rounds.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.