The Armenian made the switch to the Emirates in 2018 as part of a swap deal that saw Alexis Sanchez head to Manchester United, although the blockbuster transfer did not work out as intended for either party.
Still going strong at 35, Mkhitaryan should act as one of three midfield fulcrums in Simone Inzaghi's recognisable 3-5-2 system, spearheaded by Lautaro Martinez and Mehdi Taremi.
The former came up with the winning goal in Sunday's nervy 1-0 Serie A success over Venezia, while Taremi already has one goal and two assists under his belt from three Champions League matches this term and could displace Marcus Thuram up front.
A single alteration in the middle of the pack is also in store, as Hakan Calhanoglu should demote Piotr Zielinski to the bench as he links arms with Mkhitaryan and Nicolo Barella, flanked by Denzel Dumfries and Federico Dimarco.
Key centre-back Alessandro Bastoni was substituted with 20 minutes to go on Sunday, but the Italy international is only believed to have been suffering from cramp and should be given the thumbs-up to start on Wednesday.
Bastoni should comprise part of an unchanged backline alongside Yann Sommer, Stefan de Vrij and Benjamin Pavard, as Inter aim to keep four consecutive clean sheets in the Champions League/European Cup for the first time ever.
Inter Milan possible starting lineup:
Sommer; Pavard, De Vrij, Bastoni; Dumfries, Barella, Mkhitaryan, Calhanoglu, Dimarco; Taremi, Martinez