Tuanzebe made 11 appearances during a loan spell with Aston Villa this season, but was recently recalled by the Red Devils.
The 24-year-old central defender is on the move again after agreeing to join Serie A side Napoli.
Tuanzebe had spent two previous loan spells at Villa Park in 2018 and 2019, when the club was in the Championship, and has made 37 appearances for United.
Tuanzebe could be available to make his debut for Luciano Spalletti's side against Sampdoria on Monday (AEDT) with the club depleted because of injuries, COVID-19 cases, and Africa Cup of Nations call-ups.
Third-placed Napoli has the joint-best defensive record in Serie A this season, conceding just 15 goals in 20 games, from 16.36 expected goals against, the lowest tally in the Italian top-flight.
It has, however, struggled in the absence of influential defender Kalidou Koulibaly, who missed a month through injury before jetting off to play in the Africa Cup of Nations.
Spalletti's team has kept just one clean sheet since Koulibaly's most recent appearance, a 2-2 draw with Sassuolo in early December, and will now hope that Tuanzebe, who has represented England at three youth levels, can provide valuable cover in the heart of their backline.