A win would guarantee the Italian side a position in the knockout round of the competition, although a draw or even a defeat could be enough depending on Dortmund's result against Slavia Prague.
Inter have only beaten Barca once in their previous nine meetings, though, and the Spanish champions will bring a six-game winning run into Tuesday's fixture in Milan.
Here, Sports Mole looks at how the home side could line up in the European affair.
Inter will once again be without the services of on-loan Manchester United attacker Alexis Sanchez due to an ankle problem, while two key midfielders are also absent for the Italian side.
Indeed, Stefano Sensi is battling to overcome an abductor issue, while a knee problem will rule Nicolo Barella out of the contest in what is a huge blow for the home team.
Roberto Gagliardini is also a doubt due to a foot problem, but Inter are hopeful that Antonio Candreva will overcome a back injury in time to feature on Tuesday night.
Candreva was forced off during Friday's goalless draw with Roma, and the Italian will reportedly be monitored over the next 24 hours before a final decision on his potential involvement is made.
Kwadwo Asamoah is also an option, having made his comeback from injury against Roma, but there will be no changes in the final third as Romelu Lukaku and Lautaro Martinez prepare to continue their partnership.
Lukaku missed the chance to play against Barca earlier this season due to a suspension, but the summer arrival will be in Inter's starting XI on Tuesday night.body check tags ::