While Spurs sit in fifth position in the Premier League standings, Wycombe are seven points adrift from safety in the Championship.
Having played five games during the opening 17 days of 2021, Jose Mourinho will have been satisfied to have had a week off from action ahead of their upcoming relentless schedule.
Nevertheless, with Liverpool to come on Thursday night, it leaves the Portuguese with much to ponder regarding his team selection as he looks to progress further in this competition.
Spurs set up the last-32 tie at Adams Park with a 5-0 triumph away at Marine in a game which saw Benfica loanee Carlos Vinicius net a hat-trick.
While the 25-year-old starred on that occasion, Gareth Bale was only used as a substitute, and all eyes will be on the Welshman if, as expected, he features on Monday night.
The North Londoners head into this fixture having put together a seven-match unbeaten streak since losing to Leicester City on December 20.
A number of positive coronavirus tests means that Wycombe will play host to Mourinho's side after a 16-day absence from action.
The Chairboys have not played since their excellent 4-1 win over Preston North End in round three, the result representing just their fourth success of the season in all competitions.
Although the goals continue to be shared around this squad, the second-tier strugglers have now found the back of the net in five successive matches, their best run of the campaign.
Gareth Ainsworth is expected to name a full-strength team for this contest, but the Wycombe boss will also have one eye on the nine league games which are scheduled to be played before the end of February.
Wycombe Wanderers FA Cup form: W
Wycombe Wanderers form (all competitions): LDLWLW
Tottenham Hotspur FA Cup form: W
Tottenham Hotspur form (all competitions): DWWWDW
Mourinho has suggested that Dele Alli will miss out for Spurs with a tendon injury.
Despite his side's dominant win over Preston, Ainsworth may revert back to the players who could start against Brentford at the weekend.
Wycombe Wanderers possible starting lineup:
Allsop; Grimmer, Knight, Tafazolli, Jacobson; Thompson, Gape; Wheeler, Horgan, Onyedinma; Kashket
Tottenham Hotspur possible starting lineup:
Hart; Doherty, Sanchez, Rodon, Davies; Sissoko, Winks; Bale, Lamela, Moura; Vinicius
We say: Wycombe Wanderers 0-2 Tottenham Hotspur
While Mourinho would have preferred this game to have been played at the weekend, the Portuguese will at least be able to field players who require game time. The desire to impress should be enough for Spurs to enjoy a routine win over opponents who have struggled for goals all season.