Key centre-back Jack O'Connell has missed the majority of the season with a knee injury, while forwards Oli McBurnie and Billy Sharp have also both been ruled out for the remainder of the campaign through injuries.
Norweigan midfielder Sander Berge also suffered another injury setback recently following his return from a hamstring issue, and he could again be unavailable on Wednesday.
However, their worries have been slightly lifted with the return of Jack Robinson, who came back into the side in the left spot of a back three, which was previously occupied by O'Connell in the Blades' successful first season back in the top flight.
Robinson impressed upon his return, setting up the winning goal in the seventh minute while also playing a big role in a clean sheet against a strong Everton outfit.
The only goal of the game was scored by 17-year-old forward Daniel Jebbison on his first Premier League start, and the Canadian-born prospect could start again on Wednesday.
That is largely down to the absence of Sharp, McBurnie and Burke, while Rhian Brewster has struggled to hit the ground running in Sheffield, having failed to score for his new club since joining from Liverpool at the beginning of the season.
Jebbison could be joined in attack by David McGoldrick, who has netted seven of the Blades' 19 league goals so far this season, bringing plenty of quality and experience to the forward line.
Heckingbottom is unlikely to make any changes to the side that picked up an impressive victory over Everton on Sunday, with Ben Osborn expected to line up in the midfield again alongside Oliver Norwood and John Fleck, as John Lundstram's failed contract renewal negotiations could mean he has started his last game for the South Yorkshire outfit.
Sheffield United possible starting XI: Ramsdale; Basham, Egan, Robinson; Baldock, Osborn, Norwood, Fleck, Stevens; McGoldrick, Jebbison
Watch the Sports Mole Football Shorts prediction for this game below: