The former Rossoneri midfielder was at risk of sitting out the reunion with his former club, having picked up a thigh niggle while representing Italy during the international break.
However, Tonali was passed fit to make the bench for Saturday's 1-0 win over Brentford in the Premier League, and having been an unused substitute at St James' Park, the 23-year-old ought to be reintroduced into the starting lineup against his old employers.
Tonali's fellow lynchpins Joelinton (knee) and Joe Willock (calf) will both be forced to miss Newcastle's first Champions League game in 20 years, though, while right-back Emil Krafth is working his way back from a devastating ACL injury.
Fresh from keeping his first clean sheet of the season, Nick Pope will undoubtedly act as the last line of defence for Newcastle, most likely with Sven Botman and Fabian Schar as the central barrier after the former shook off a knock of his own.
Kieran Trippier can expect a taxing evening against Rafael Leao out wide, while Dan Burn should continue on the left-hand side, where either Christian Pulisic or Samuel Chukwueze will be testing his defensive mettle.
Tonali's imminent comeback should see Elliot Anderson demoted to a bench role, as Bruno Guimaraes and Sean Longstaff join the Italian in Eddie Howe's midfield triumvirate, but the Magpies boss is facing more than one selection dilemma up top.
Callum Wilson's penalty was the difference against Brentford, but Alexander Isak will be expected to spearhead the attack, while Anthony Gordon and Harvey Barnes both impressed against the Bees and could keep an under-performing Miguel Almiron at bay once more.
Newcastle United possible starting lineup: Pope; Trippier, Schar, Botman, Burn; Longstaff, Tonali, Guimaraes; Gordon, Isak, Barnes