The Nerazzurri were held to a pulsating 2-2 draw by Borussia Monchengladbach at home on the opening day as a brace from Romelu Lukaku salvaged a point.
Donetsk, however, are flying high after pulling off one of their biggest upsets in recent European history, beating Real Madrid 3-2 in the Spanish capital.
Tete and Manor Salomon struck in the first half on either side of Raphael Varane's own goal to put the former champions to the sword and send shockwaves across the continent with an unlikely triumph.
A similar result on Tuesday would boost the knockout round hopes of the Ukrainian champions.
Shakhtar Donetsk vs Inter Milan Head-To-Head
In only three previous meetings between the sides, Inter Milan have emerged victorious twice, including the 5-0 thrashing in the semi-finals of the Europa League in August this year.
Their only previous clash came way back in 2005 when they were drawn against each other in the Champions League qualifiers, with the Serie A giants progressing into the tournament proper after winning 3-1 on aggregate.
Shakhtar Donetsk Form Guide (all competitions): W-D-W-W-D
Inter Milan Form Guide (all competitions): W-D-L-D-W
Shakhtar Donetsk vs Inter Milan Team News
The hosts don't have Maksym Malyshev back yet, are he underwent knee surgery over a year ago, whereas Ismaily and Yevgen Konoplyanka will only return in December.
Sergiy Kryvtsov and Viktor Kovalenko will also miss out, whereas Junior Moraes continues to recover from COVID-19.
Injured: Maksym Malyshev, Ismaily, Yevgen Konoplyanka, Sergey Kryvtsov, and Viktor Kovalenko
Unavailable: Junior Moraes
Inter Milan have a few absentees too, as Matias Vecino is still recuperating from his knee injury, while Milan Skriniar, Roberto Gagliardini, and Ionut Radu are still in isolation after testing positive for COVID-19 in the second week of October.
One bit of good news for the visitors, though, is that Achraf Hakimi has successfully recovered from the virus, and after coming off the bench at the weekend in Genoa, should slot right back into Tuesday's starting XI.
Injured: Matias Vecino
Unavailable: Ionut Radu, Milan Skriniar, and Roberto Gagliardini
Shakhtar Donetsk vs Inter Milan Predicted XI
Shakhtar Donetsk (4-1-4-1): Anatoliy Trubin; Dodo, Valeriy Bondar, Davit Khocholava, Viktor Kornienko; Maicon; Tete, Marlos, Marcos Antonio, Manor Solomon; Dentinho.
Inter Milan (3-4-1-2): Samir Handanovic; Danilo D'Ambrosio, Stefan de Vrij, Aleksandar Kolarov; Achraf Hakimi, Nicolo Barella, Arturo Vidal, Ivan Perisic; Christian Eriksen; Romelu Lukaku, Lautaro Martinez.
Shakhtar Donetsk vs Inter Milan Prediction
Shakhtar, with their confidence boosted after the Madrid shocker, may fly out of the blocks once again to put the Nerazzurri on the back foot, but Antonio Conte's side have plenty in the tank to eke out at least a draw. Expect another high-scoring affair though, and perhaps a stalemate at the end of 90 minutes.
Prediction: Shakhtar Donetsk 2-2 Inter MilanPublished 25 Oct 2020, 19:22 IST