The tie will now be a one-legged affair on neutral soil in Gelsenkirchen after the original meeting between the sides in March was called off by the coronavirus pandemic.
Either Rangers or Bayer Leverkusen await the winners off this match in the quarter-finals of the condensed tournament, which will be played out over the next three weeks.
Inter head into Wednesday's match with serious questions being asked of boss Antonio Conte's future, with reports in Italy suggesting that he will not survive a second season.
That may seem remarkable on the face of it, with the Nerazzurri ending the Serie A campaign strongly to finish just a point behind nine-in-a-row champions Juventus.
However, Conte has been a collision course with his own bosses over a lack of support both in terms of transfers and in the media, which could see him move on this summer.
Any change in the dugout is unlikely to take place before the reformatted Europa League concludes, with Conte relying on this competition to provide him with some silverware.
Inter, despite the off-field issues, head into this match with Getafe in good form thanks to three wins in a row to conclude their domestic campaign.
The Nerazzurri have lost just one of their 14 matches post-lockdown, meanwhile, and are considered the favourites to win UEFA's secondary competition.
However, while they may have seen off Ludogorets fairly comfortably in the last round, Inter have a pretty poor record when it comes to beating Spanish opposition.
They have won just one of their last 12 such encounters and are winless since a 3-1 victory against Barcelona in the 2009-10 Champions League semi-final.
Whether the winner-takes-all-nature of this last-16 tie will suit Inter remains to be seen, but they will certainly fancy their chances against an out-of-form Getafe side.
Jose Bordalas's men knocked Dutch heavyweights Ajax out of the competition in the last round, but they have managed just one win in 11 matches since returning to action in June.
That includes a run of three defeats and two draws to conclude the La Liga season, seeing them slip down to eighth, just outside a European spot.
Bordalas has had a couple of weeks to drill his side ready for this one-off showdown with Inter, though, and his side have certainly caught the eye on the continent this term.
Only Sevilla (5), Basel (6) and Manchester United (7) have kept more clean sheets in this seasons Europa League than Getafe (4), who showed real grit to overcome much-fancied Ajax.
Getafe are playing against a Spanish side for the first time and are aiming to reach the quarter-finals of this competition for a second time, having done so in 2007-08.
Inter Milan's Europa League form: WWDLWW
Inter Milan's form (all competitions): WDDWWW
Getafe's Europa League form: LLDDDLL
Getafe's form (all competitions): LDLDLL
However, Alexis Sanchez is another option up top in what could be his final game for the club before returning to parent club Manchester United, or indeed all three could start.
Getafe will be without centre-back Erick Cabaco on Wednesday as he only joined in January and has not been registered to play.
Elsewhere, Stoke City loanee Oghenekaro Etebo is recovering from injury and is unlikely to feature in the one-legged tie.
Inter Milan's possible starting lineup:
Handanovic; Godin, De Vrij, Bastoni; Candreva, Eriksen, Brozovic, Young; Sanchez; Lukaku, Martinez
Getafe possible starting lineup:
Chichizola; Suarez, Dakonam, Etxeita, Olviera; Nyom, Arambarri, Maksimovic, Cucurella; Rodriguez, Mata
We say: Inter Milan 2-0 Getafe
Had this game been played when originally intended in March, Getafe would have fancied their chances of pulling off an upset. The Spanish club will still give it a real go, of course, but the form of the two sides post-lockdown has been massively contrasting and we expect Inter to progress.