The hosts have won only one of their last 12 matches, while Morecambe have recorded just one victory in their previous seven games.
Match preview
Cambridge fell to a third consecutive defeat without scoring when they were beaten 1-0 at home to Portsmouth on Saturday.
As a result of the narrow loss, the U's languish in 23rd place and are five points adrift of Accrington Stanley, who sit just outside the bottom three and have two games in hand over Cambridge.
Mark Bonner's side are the joint lowest scorers in the third tier - alongside Cheltenham Town - with 26 goals in 34 matches, highlighting a goalscoring issue which needs to be solved if they are to escape the drop zone.
Having collected 21 of their 29 points at the Abbey Stadium this season, Bonner will also be aware that Cambridge's home games will be crucial in the League One run-in.
Although confidence may be low in the Cambridge squad, they can draw inspiration from the fact that they have won their last five meetings with Morecambe, including a 2-1 away victory when the two sides met in September.
Morecambe, meanwhile, head into the midweek encounter in 21st place and two points adrift of Accrington, who have also played two games less than the Shrimps.
Derek Adams's side were unable to record a home victory on Saturday, but they managed to hold fourth-placed Bolton Wanderers to a goalless draw.
As a result, Morecambe now only lost one of their last 12 home matches, but they have been unable to transfer that impressive form onto their travels.
Having picked up just seven points from their 16 away league games this season, the Shrimps currently hold the worst away record in the third tier.
Their sole away victory of the League One season took place against Forest Green Rovers in September, and since that result, Morecambe have only managed to collect two points from 11 away matches.
Cambridge United League One form:
L
L
W
L
L
L
Morecambe League One form:
D
L
L
W
L
D
Team News
Cambridge will be without the services of January arrival George Thomas, who has been ruled out for the rest of the season with an ankle injury.
After sustaining an injury on his Cambridge debut in January, Steve Seddon returned to the squad to feature as a late substitute against Portsmouth, and he could be brought into the starting lineup for Tuesday's contest.
With six league goals apiece this season, Joe Ironside and Sam Smith will offer the goal threat for the hosts when they both feature in a front two.
As for the visitors, they are expected to be without the services of Michael Mellon for a second straight game due to an injury issue.
Adam Mayor dropped out of the lineup for Saturday's goalless draw, but the 17-year-old could return to the starting XI in midweek.
After missing Morecambe's 1-0 defeat to Fleetwood Town through injury Cole Stockton returned to the side at the weekend, and he will continue to lead the line against Cambridge.
Cambridge United possible starting lineup:
Mitov; Morrison, R. Bennett, Jones; L. Bennett, McGrandles, Digby, Seddon; Lankester; Ironside, Smith
Morecambe possible starting lineup:
Ripley; Love, Rawson, Bedeau, Melbourne; Shaw, Gibson; Weir, Crowley, Mayor; Stockton