The hosts recorded a 3-2 victory over Fulham Under-21s in the previous round of the competition, while West Ham Under-21s advanced courtesy of a 4-0 success over Colchester United.
Match preview
Wycombe will enter this contest off the back of a 1-1 draw with Burton Albion on Saturday, with the result leaving them in 16th position in the League One table on 29 points.
Matt Bloomfield's side are unbeaten in their last three matches, while they have lost just one of their last six matches in all competitions, so the home team will enter this match in strong form.
The Chairboys have won each of their four matches in this season's EFL Trophy, beating Crystal Palace Under-21s, Stevenage and AFC Wimbledon all 1-0 in the group stage of the tournament.
Wycombe were paired with Fulham Under-21s in the last round of the competition and managed to record a 3-2 victory, with Dale Taylor netting twice and Christian Forino-Joseph also on the scoresheet.
The Chairboys are next in League One action against Lincoln City on Saturday afternoon, and the quick turnaround from the Burton clash makes this a tough assignment against a talented outfit.
West Ham Under-21s, meanwhile, will enter this match off the back of three straight wins in all competitions, including a 4-0 success over Colchester in the last round of the tournament.
Steve Potts's side have since been in action in Premier League 2, thumping Crystal Palace Under-21s 5-1, with the result leaving them second in the table, boasting 23 points from 10 matches.
West Ham Under-21s have won seven of their last eight matches in all competitions, while they are unbeaten since a 3-0 reverse at Arsenal Under-21s in Premier League 2 on August 11.
Potts's team beat Bristol Rovers, Newport County and Cheltenham Town in the group stage of this season's EFL Trophy, and they have only conceded once in the competition this term, scoring 12 times in the process.
Wycombe will have the experience, but West Ham Under-21s have proved themselves to be a very strong outfit, and it will be a fascinating contest in the last-16 stage of the Southern section.
Wycombe Wanderers EFL Trophy form:
W
W
W
W
Wycombe Wanderers form (all competitions):
D
D
L
D
W
D
West Ham United Under-21s EFL Trophy form:
W
W
W
W
West Ham United Under-21s form (all competitions):
W
W
W
W
W
W
Advert - content below:
Team News
Wycombe head coach Bloomfield is not expected to make many changes to the side that took to the field for the first whistle against Burton in League One on Saturday afternoon.
Franco Ravizzoli will come in between the sticks, while Sam Vokes could drop out in the final third, but it will be a familiar side, with Taylor set to be among the starters.
Taylor scored twice against Fulham Under-21s in the last round of the competition, and he could be joined in a forward area by Gareth McCleary and David Wheeler.
As for West Ham Under-21s, Ben Johnson was involved off the bench against Bristol City in the FA Cup on Sunday, but there is a chance that he could feature here.
Johnson started against Colchester in the last round of the EFL Trophy, as did Conor Coventry, and the midfielder is also set to feature, having not been used off the bench in the FA Cup.
Divin Mubama came on early against Bristol City due to an injury for Lucas Paqueta, but the striker is in line to feature from the first whistle in this contest.
Wycombe Wanderers possible starting lineup:
Ravizzoli; Grimmer, Keogh, Jacobsen; Sadlier, Breckin, Leahy, Boyes; McCleary; Wheeler, Taylor
West Ham United Under-21s possible starting lineup:
Anang; Chesters, Johnson, Casey, Luizao, Scarles; Earthy, Coventry, Kelly; Marshall, Mubama
We say: Wycombe Wanderers 1-2 West Ham United Under-21s
This is set to be a fascinating watch, and we are expecting it to be a close match on Tuesday, but it is difficult to ignore the away team's form. West Ham Under-21s have so much talent in the forward areas, and we are backing them to advance in the competition courtesy of a narrow success.