Barca have already booked their spot in the knockout round as group winners, but Inter are battling Borussia Dortmund for the second qualification spot.
Inter's task is actually quite simple; win and they would be guaranteed a spot in the knockout round of the competition. Antonio Conte's side could also lose and still go through providing that Dortmund do not pick up a draw or better against Slavia Prague in the section's other fixture.
Both Inter and Dortmund have seven points to show from their five matches, but the Italian side are second on the head-to-head record, meaning that Dortmund will have to rely on Barca picking up a result if the Bundesliga giants are to sneak into the last-16 stage of the tournament.
Inter picked up a 1-1 draw when they last welcomed Barca to San Siro during the group stages of the 2018-19 competition. They have only won one of the nine meetings between the two teams, though, which came on home soil during the semi-finals of the 2009-10 tournament, where they won the trophy under Jose Mourinho.
Conte's side have beaten Dortmund at home and Slavia Prague away in this season's group stage, but they suffered a 2-1 loss away to Barca at the start of October and also lost 3-2 away to Dortmund last month.
As a result, the Italian giants have only won two of their last nine Champions League matches. That said, they have won five of their last nine European games on home soil, suffering just one defeat in the process.
The Milan outfit could not overcome Roma on Friday night as they were held to a goalless draw, but a brilliant start to their 2019-20 Serie A campaign has left them top of the table, two points clear of the champions Juventus.
Romelu Lukaku and Lautaro Martinez have formed an impressive partnership in the final third of the field, and both players will surely need to be at their best if the hosts are to pick up a positive result on Tuesday.
The Nerazzurri are unbeaten in their last nine matches with La Liga opposition on home soil, although they have recorded just three wins during that run. A point could be enough to book their spot in the next round but with Dortmund expected to triumph on home soil in the other match, Inter might well have to beat Barca to make the round of 16.
Recent form (Champions League): DLWLW
Recent form (all competitions): LWWWWD
There is no pressure on Barca heading into Tuesday's contest as a 3-1 win over Dortmund at Camp Nou on November 27 ensured that they would be present in the round of 16 as group winners.
Ernesto Valverde's side have not been at their best in the section, but a record of three wins and two draws from five matches has brought them 11 points, leaving them four clear of second-placed Inter as things stand.
Barca will actually bring a six-game winning run into this match having continued their fine form with a 5-2 success at home to Mallorca on Saturday night. Lionel Messi scored another hat-trick for the reigning champions, who are top of La Liga, just ahead of Real Madrid on goal difference.
The Catalan giants have not always shown their best form this season, but Messi appears to be back to his best after overcoming some injury issues earlier in the campaign. The Argentina international, who was crowned the 2019 Ballon d'Or winner last week, has managed 14 goals in 15 appearances at club level this season.
Barca have not failed to qualify for the knockout round of the Champions League since the 2000-01 season, while they have reached the last-16 stage or better in each of their last 16 campaigns. In total, the club have won this competition on five occasions, with their last success coming in 2015.
Many fancied Valverde's side to lift the title last season, but they were stunned by eventual winners Liverpool in the semi-finals of the competition. It does appear to be an open tournament once again, although Messi's presence means that the Spanish outfit must be considered among the favourites.
Barca have a mixed record away to Serie A opposition, winning six, drawing 11 and losing seven of their 24 matches. As mentioned, though, there is no real pressure on the team entering this match. Dortmund will be hoping for a favour, but Inter will certainly be fired up to pick up a positive result.
It will be fascinating to see whether Valverde decides to shuffle his pack for the European encounter, particularly when considering that Barca will face Real Sociedad next weekend before the small matter of El Clasico at home to Real Madrid on December 18, which is shaping up to be a fascinating encounter.
Recent form (Champions League): DWWDW
Recent form (all competitions): WWWWWW
Inter will again be without the services of on-loan Manchester United attacker Alexis Sanchez due to an ankle injury, while Conte will also be unable to call upon two key midfielders.
Arthur is struggling to overcome an adductor issue, while Fati is battling a knee problem, meaning that neither are expected to be involved at San Siro.
Luis Suarez could be rested with the Uruguay international having his fair share of injury problems this season, although Messi is expected to continue in the final third of the field.
Inter Milan possible starting lineup:
Handanovic; Godin, De Vrij, Skriniar; Biraghi, Valero, Brozovic, Vecino, Candreva; Martinez, Lukaku
Barcelona possible starting lineup:
Ter Stegen; Roberto, Umtiti, Lenglet, Firpo; De Jong, Vidal, Rakitic; Perez, Messi, Griezmann
Head To Head
Barca lead the head-to-head record five wins to Inter's one, with the pair also playing out three draws.
The Spanish giants recorded a 2-1 win over Inter in the reverse match earlier this season, while Inter's sole victory in this fixture came on home soil in the semi-finals of the 2009-10 tournament.
Barca have actually never won a European match away to Inter, although they have suffered just one defeat, picking up three draws in the process.
We say: Inter Milan 1-1 Barcelona
It would not be a surprise if Inter triumphed on Tuesday night, but a Barca victory would also not be a shock due to their recent form. We are finding it difficult to separate them, though, and fancy Inter to pick up a point which might well be enough to book their spot in the knockout round of the competition.