The England midfielder has not played since the club's 0-0 draw with Brighton & Hove Albion on February 13 due to a shin injury, with the 25-year-old recently suffering a setback in his recovery from the issue.
Villa boss Dean Smith admitted that "we all, Jack included, probably pushed him back a little too quickly," and that it could be another couple of weeks before he features for the first team.
The Villains have also lost Trezeguet for the rest of the campaign after the Egypt winger sustained a serious knee injury in the 2-1 defeat to Liverpool last time out.
The 26-year-old left the field in tears after 82 minutes following an innocuous challenge with Liverpool full-back Trent Alexander-Arnold, but it has been confirmed that Trezeguet will undergo surgery as a result.
Anwar El Ghazi is likely to replace the Egyptian on the left flank from the side which narrowly lost at Liverpool, but otherwise Smith could name an unchanged XI as he looks to pack the midfield once again with the industry of John McGinn, Douglas Luiz and Marvelous Nakamba in an attempt to combat Man City's talent in that area of the pitch.
Wesley is nearing a return to first-team action for the first time since January 2020 after recovering from his serious knee injury, but Wednesday's test against Pep Guardiola's league leaders is likely to come too soon for the striker.
Midfielder Morgan Sanson should return to the matchday squad, though, having been rested for the trip to Anfield due to a minor knock to his knee.
Aston Villa possible starting lineup: Martinez; Cash, Konsa, Mings, Targett; McGinn, Luiz, Nakamba; Traore, Watkins, El Ghazi