In the midst of a hectic Premier League schedule, Dean Smith and Nuno Espirito Santo look set to ring the changes ahead of the 136th meeting between the two West Midlands sides.
Whilst it may only be the ninth time the two have met as top-flight clubs since the turn of the millennium, star players are likely to be rested for this meeting.
Dean Smith has made a total of 19 alterations from Premier League games before Villa claimed victory over Crewe and Brighton in the last round by an aggregate score of 9-2.
Defence
Jed Steer looks certain to retain his Carabao Cup place with Tom Heaton potentially left our the squad altogether. Orjan Nyland will made up the numbers on the Villa bench for both round two and three cup ties.
With the strong possibility of a penalty shoot out on the cards, Steer's expertise between the sticks could prove the difference for Villa. They managed to squeeze past another West Midlands rival, West Brom, to reach the play-off final last season.
Elsewhere in defence, Smith may opt to swap both full-backs for the visit of Wolves. Ahmed Elmohamady and Neil Taylor have both played their part in this seasons Premier League campaign but new arrivals Frederic Guilbert and Matt Targett have since pinned down their respective places.
Kortney Hause could well start against the club he initially left on loan before making a switch to Villa permanent from Molineux last summer. Alongside Ezri Konsa, the two have started both League Cup matches this season. Smith may, however, decide to involve one of Bjorn Engels or Tyrone Mings from his tried and trusted duo.
Midfield
Villa's depth in midfield positions has worked well for Smith so far this term, but with the injury sustained to Jack Grealish's calf in the defeat at the Etihad Stadium last week, Villa's captain will be unavailable. After impressing against his former club Man City, Douglas Luiz looks likely to retain his place with Conor Hourihane and Henri Lansbury alongside the Brazilian.
Marvelous Nakamba's energy and enthusiasm may be rested ahead of Liverpool's visit on Saturday.
Where Villa may lack in experience on Wednesday, Dean Smith will surely make up for it with some youthful exuberance. Jacob Ramsey may get his chance off the bench. The 18-year-old has continued to impress Smith in first team training. The Villa youngster has made one appearance for Villa this campaign, a ten-minute cameo in the third-round win at the Amex Stadium. The attacking midfielder made his debut in a home defeat to West Brom in the Championship last season.
Attack
Further forward, Trezeguet and Anwar El Ghazi look certain to occupy the flanks and supply Keinan Davis in attack. Egyptian international Trezeguet has shown nothing more than glimpses since his £9 million move from Kasimpasa in August.
He is yet to contribute with a goal involvement this term. El Ghazi has however made six contributions in all competitions this season, including an assist in round two at Gresty Road. Davis registered his first of the season in the 6-1 rout at Crewe, whilst assisting in Brighton.
Villa host Wolves on Wednesday, 19:45 kick-off.
