The Catalan giants have already overcome PSV Eindhoven and Tottenham Hotspur in their first two outings, leaving them on six points from six at the top of Group B.
Inter have also picked up maximum points against the same opponents, however, meaning that it is all to play for in this high-profile showdown in Catalonia.
Ahead of Wednesday's match, Sports Mole looks at how Ernesto Valverde may set out his side.
Barca were rocked at the weekend with news that star man Messi, who has netted five goals across Barca's opening two European fixtures this term, is facing three weeks on the sidelines with a fractured arm.
Valverde therefore has a big decision to make with regards to his formation and personnel, with Ousmane Dembele and Philippe Coutinho - also on the scoresheet for Barca in the early stages of the Champions League - likely to get the nod either side of Luis Suarez in a 4-3-3 setup.
Centre-back remains a problem area for the Spanish champions, who are having to rely on Clement Lenglet alongside the overused Gerard Pique for the foreseeable future, as Umtiti and Vermaelen both remain on the sidelines.