While the home side are three points adrift of safety, Wanderers travel to Hillsborough 12 points behind 21st-placed Derby County.
When Sheffield Wednesday went ahead at Millwall on Saturday afternoon, caretaker boss Neil Thompson would have felt that his Owls side were well on their way to another important three points.
However, their second-half capitulation at The Den has put a different spin on things, with Wednesday now three points adrift of safety with their goal difference having taking a significant hit courtesy of the 4-1 defeat.
Conscious that he can have few complaints with the progression of his side in recent weeks, Thompson will hope that the setback is a minor blip in their bid to avoid relegation.
Nevertheless, with a second successive defeat putting them at risk of losing touch with the teams above them, there is now pressure on his players to perform against the weakest side in the division.
Thompson will also feel that he may only be one more negative result away from the end of his temporary spell in charge, despite five wins from eight matches coming in all competitions.
With 20 matches still remaining in the season, Wycombe are not quite at the point of no return if they suffer their 17th defeat of the campaign on Tuesday night.
That said, having collected just one point from games against Birmingham City and Nottingham Forest, Gareth Ainsworth knows that a momentum change is needed at Adams Park.
Failing to score during either of those matches frustrated the Chairboys boss, who would have felt that progress was being made in the final third of the pitch.
Wycombe emerged victorious by a 1-0 scoreline in the reverse fixture back on October 31, a result which represented their first ever victory in the second tier.
Sheffield Wednesday Championship form: WWLWWL
Sheffield Wednesday form (all competitions): WLLWWL
Wycombe Wanderers Championship form: LWLLDL
Wycombe Wanderers form (all competitions): LWLLDL
Having suggested that some of his players were feeling the effects of a tough schedule, Thompson is expected to make changes to his Wednesday XI.
Sheffield Wednesday possible starting lineup:
Westwood; Lees, Dunkley, Urhoghide; Palmer, Reach, Bannan, Pelupessy, Harris; Paterson, Rhodes
Wycombe Wanderers possible starting lineup:
Allsopp; Grimmer, Stewart, Tafazolli, McCarthy; Wheeler, Ofoborh; Horgan, McCleary, Muskwe; Ikpeazu
We say: Sheffield Wednesday 2-0 Wycombe Wanderers
Both teams will view this fixture as the ideal opportunity to respond to their respective setbacks at the weekend. Nevertheless, we can only see a comfortable home win, a result which would leave Wycombe further cut adrift at the bottom of the table.