Both sides have seen off Viktoria Plzen but lost to Bayern Munich, but the hosts have endured their worst Serie A start for 11 years while their Catalan counterparts are unbeaten in seven La Liga games to date.
Match preview
Not for the first time this season, an Inter lead was overturned at the weekend, as Simone Inzaghi's side let slip a one-goal advantage to lose 2-1 at home to Roma.
A first loss to the Giallorossi since 2017 leaves them stranded adrift of Serie A's top six, and suffering four defeats in eight matches equals the Milan club's slowest start to a season throughout their top-flight history.
Again ponderous on the ball, Inter clearly missed the absent Marcelo Brozovic and Romelu Lukaku, but another setback means support for Inzaghi is slowly draining away among the Nerazzurri's fanatical fanbase.
One of five victories this term came last time out in the Champions League, as they got off the mark in a competitive Group C by beating Czech champions Viktoria Plzen 2-0, with Edin Dzeko and Denzel Dumfries scoring either side of their hosts going down to 10 men.
Previously, they had lost by the same scoreline at home to Bayern, but they have tended to fare much better at San Siro in recent times: before their setback against Roma, they had won each of their last seven home games in the league - keeping four clean sheets in the process.
As Inter have won only once from five meetings with Barcelona in Milan, though, they will need to overcome precedent to pick up maximum points this week. There is every chance Bayern will sprint into the distance by sweeping past Plzen, so back-to-back matches against the Blaugrana could be decisive.
Having failed to make it through the group stage of last season's Champions League, finishing third behind Bayern and Benfica, a rejuvenated Barcelona will not want to suffer the same fate again.
It is now seven years since they last lifted the continent's top trophy, but recent events suggest Xavi's current crop could be among the contenders to prevail in Istanbul next June.
Thanks to some slick accounting manoeuvers, the Catalan giants were able to add a number of players to their squad over the summer, including star striker Robert Lewandowski, who scored again on Saturday - his ninth goal of the season proving the difference versus Mallorca.
Barcelona are therefore battling it out with old rivals Real Madrid at the top of La Liga, and have now won six successive league matches since drawing on the opening day.
Before the international break, though, they succumbed to Bayern, with former Allianz Arena hero Lewandowski left ruing several missed chances against his erstwhile employers. That 2-0 loss in Bavaria represented Barca's fifth defeat in their last nine group-stage games.
Nonetheless, with six points on offer across both fixtures between the Blaugrana and Inter over the coming days, there is all to play for - and the contrast in confidence between both camps could prove a major factor.
Inter Milan Champions League form:
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W
Inter Milan form (all competitions):
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Barcelona Champions League form:
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Barcelona form (all competitions):
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Team News
Due to a thigh injury sustained on international duty, Inter will once again be without midfield fulcrum Marcelo Brozovic on Tuesday. Since the start of last season, the Nerazzurri have won 69% of their Serie A matches with the Croatian playmaker on the pitch; in four without him, they have failed to win once.
In addition to Brozovic's absence, Romelu Lukaku remains on the road to recovery from a thigh injury, so Edin Dzeko and Joaquin Correa fight it out to partner Lautaro Martinez up front in Simone Inzaghi's favoured 3-5-2 formation.
Hakan Calhanoglu returned from the start and struck the crossbar with a thunderous free kick on Saturday, so should feature in midfield, while Henrikh Mkhitaryan will compete for selection with Kristjan Asllani and Roberto Gagliardini to join the Turkey international and Nicolo Barella.
In goal, club captain Samir Handanovic's performances have come under scrutiny, so Andre Onana should be handed another Champions League opportunity.
Barcelona, meanwhile, travel to Italy without Memphis Depay, Frenkie De Jong and Jules Kounde, after they each picked up injuries in the Nations League last month.
Ronald Araujo may miss the rest of 2022 after undergoing thigh surgery, while Hector Bellerin is sidelined by a calf problem sustained in training last week. As a result, either Sergi Roberto or Alex Balde must fill in at right-back.
Pedri and Raphinha are likely to come back into the starting XI after starting Saturday's game on the bench, as Xavi continues to rotate his resources amid a packed schedule leading towards the World Cup.
Inter Milan possible starting lineup:
Handanovic; Skriniar, Acerbi, Bastoni; Dumfries, Barella, Asllani, Calhanoglu, Dimarco; Martinez, Dzeko
Barcelona possible starting lineup:
Ter Stegen; Roberto, Christensen, Garcia, Alba; Kessie, Busquets, Pedri; Dembele, Lewandowski, Raphinha
We say: Inter Milan 1-2 Barcelona
Defensively vulnerable and often unable to hold on to a lead, Inter are ripe for the taking this week, and Barcelona's much-improved squad are well placed to take three points home from San Siro.