After his retirement as a footballer, Martusciello returned to Empoli, this time as a youth coach. He was then promoted as assistant under Alfredo Aglietti, then Maurizio Sarri and, lastly, Marco Giampaolo. In the summer of 2016, he was named new head coach of Empoli for the upcoming 2016–17 Serie A campaign, in what it was his first role as a head coach outright. He completed the season with Empoli relegated on the final matchday, which led to him leaving the club. He was successively appointed as technical collaborator of Luciano Spalletti at Inter Milan. Spalletti was relieved from his duty as Inter's head coach in June 2019 and subsequently, Mastusciello joined the staff of newly appointed Juventus head coach Maurizio Sarri as an assistant manager. For the first two matches of the 2019–20 season, Martusciello took the lead on the bench with Sarri out due to pneumonia.