The winners of this contest will take on either Manchester United or Sevilla, who meet in the other last-four contest on Sunday.
With over half of their European fixtures having been against Spanish and German opposition this season, Inter have certainly not been provided with the easiest of times on the continent.
However, despite having been edged out by Barcelona and Borussia Dortmund in the Champions League, Antonio Conte's side have responded with victories over the likes of Getafe and Bayer Leverkusen in this competition.
After a late rally to claim the runners-up spot in Serie A, Conte is now two wins away from having had an outstanding first campaign at San Siro during what has been a period of transition for the club.
While Inter have undoubtedly benefitted from Romelu Lukaku's 31 goals, Conte has not been shy in making full use of a widely-talented squad, giving his side an extra edge heading into the closing stages of Serie A and this competition.
Nevertheless, despite justifiably being regarded as the marginal favourites ahead of Man United, I Nerazzurri cannot afford any complacency against a Shakhtar side which may relish their tag of underdogs.
Luis Castro has only been in charge of this group of players for 14 months, but the Portuguese has already guided Shakhtar to their best European effort since 2016.
Having agonisingly missed out on a place in the knockout stages of the Champions League, the Ukrainian giants have responded with entertaining victories over Benfica, Wolfsburg and Basel respectively.
Like Lukaku's role at Inter, Shakhtar have a talisman in Junior Moraes who is clear in the scoring charts with six strikes in Europe this campaign, with regular support coming from many of the club's creative players.
While recording back-to-back triumphs over Inter and either United or Sevilla would be regarded as a monumental shock, do not write off the Hirnyky after they found the back of the net on seven occasions in their last two outings.
Inter Milan Europa League form: WWWW
Inter Milan form (all competitions): DWWWWW
Shakhtar Donetsk Europa League form: WDWWW
Shakhtar Donetsk form (all competitions): WWWDWW
Inter will have to make do without Alexis Sanchez after the Chile international suffered a muscular injury in training.
Matias Vecino also finds himself out of contention, putting Conte in a position where he may select the same starting XI.
Castro will welcome Davit Khocholava back into his Shakhtar squad after the Georgian completed a ban.
However, after the manner of the win over Basel, Castro could opt to retain the same side.
Inter Milan possible starting lineup:
Handanovic; Godin, De Vrij, Bastoni; D'Ambrosio, Barella, Brozovic, Gagliardini, Young; Martinez, Lukaku
Shakhtar Donetsk possible starting lineup:
Pyatov; Dodo, Krivtsov, Bondar, Matvyenko; Antonio, Stepanenko; Marlos, Patrick, Taison; Moraes
We say: Inter Milan 3-1 Shakhtar Donetsk
While we expect plenty of action at both ends of the pitch on Monday night, Inter's extra bit of quality in defence and attack should combine to help them see off a Shakhtar outfit whose superb run in the competition may come to an end.