Antonio Conte's side returned to winning ways with a 4-0 win over Leeds at the weekend to leave them seventh in the Premier League table.
Spurs are out of Europe as well meaning the FA Cup represents the club's last chance at ending their long wait for silverware this season.
But Middlesbrough provides a potential banana slip fixture with the Championship outfit eliminating Manchester United in the last round.
Boro are eighth in the Championship and lost at Barnsley at the weekend
Middlesbrough vs Tottenham: talkSPORT commentary
This FA Cup fifth round clash will take place on Tuesday, March 1.
talkSPORT 2 will have live coverage of the match at the Riverside Stadium at 7:55pm.
Commentary will come from Ian Danter and former Leeds Women's striker Lucy Ward.
Tottenham beat Brighton 3-1 at home in the previous round while Boro stunned United on penalties at Old Trafford following a 1-1 draw.
To tune in to talkSPORT or talkSPORT 2, click HERE for the live stream.
App iPhone - Download from the Apple store
Android - Download from Google Play
Radio - talkSPORT is available across the United Kingdom via DAB digital radio and on 1089 or 1053 AM
TV - Listen to talkSPORT through your TV on the following channels: Sky: Channel 0108 Virgin Media: Channel 927 Freeview: Channel 723 Freesat: Channel 731
Middlesbrough vs Tottenham: Team news
The hosts are without Marc Bola due to a knee injury, but Matt Crooks is back from suspension and is available.
Boro have an otherwise clean bill of health and Arsenal loanee Folarin Balogun is once again expected to start in attack.
Spurs meanwhile have a number of injuries to contend with as Rodrigo Bentancur, Oliver Skipp, Lucas Moura and Japhet Tanganga are all out.
But Sergio Reguilon returned to the bench against Leeds and could earn a start if Conte freshens up his starting XI.
Middlesbrough vs Tottenham: What has been said?
Conte discussed having four academy players on the bench at Elland Road in his pre-match press conference.
He said: "I don't give gifts to my players. If you are a player and you are only 17-years-old, Dane (Scarlett's) working really hard and he is a really good prospect from the academy.
"He is for sure at this moment the best prospect from the academy. There are a couple of others who are improving.
"Dane has to continue to work very hard, we are trying to find the best solution in the training because he has a long history with injuries, he has great potential, he is only 17.
"I don't give gifts to anybody, they have to deserve this opportunity."