A win for Boro will see them leapfrog Stoke in what is becoming an increasingly tight top half, with only eight points separating the 12 sides.
A Nick Powell header was enough for Stoke to take away all three points in midweek as they overcame a blunt Wycombe Wanderers side, struggling at the bottom of the Championship.
The win leaves the Potters eighth in the table and they will be keen to kick-on in the hope of mounting a robust promotion challenge.
A win on Saturday will require Stoke to put to bed a poor recent record against Boro, though.
City have lost their last three league matches against Middlesbrough, their worst such losing run against them since a run of three between 1938 and 1946.
The Bet365 has seen many a goal so far this season with 26 flying in at either end - more than any other ground in the competition.
Former Sunderland man Watmore only signed for Boro three weeks ago but has seemingly made a strong first impression on Neil Warnock judging by the glowing comments that followed the home win against Swansea.
His first goals for the club were enough to see off the Swans, with Boro now sitting top of the home form table with 17 points from their eight games at the Riverside.
Boro's stern defence has been their standout strength so far this campaign, and they will be keen to banish any memory of the three goals they conceded in their last away league game against Huddersfield Town - as many as they had shipped in their first six on the road in the Championship this season.
Boro boss Warnock turned 72 this week and though the win against Swansea would have been an appropriate birthday present, a win at Stoke really would be the icing on the cake.
Warnock has won his last three away league matches against Stoke, having won none of his first five there between 1997 and 2006. Boro are also looking to win consecutive away league matches against Stoke for the first time since March 1956.
Stoke City Championship form: LWWLDW
Middlesbrough Championship form: DDLWLW
O'Neill will be hoping that Ryan Shawcross will be ready to feature having come through numerous Under-23 fixtures unscathed, but will likely be without Steven Fletcher and Lee Gregory, while John Obi Mikel is a major doubt.
Warnock will again be without recent signing Grant Hall as he experienced a setback to his recovery earlier in the week.
Otherwise, Warnock now has a full squad to choose from, given Sam Morsy's return to action.
Stoke City possible starting lineup:
Bursik; Collins, Chester, Batth, Fox; Cousins, Clucas; Campbell, Powell, Brown; Vokes
Middlesbrough possible starting lineup:
Bettinelli; Dijksteel, McNair, Fry, Bola; Tavernier, Howson, Saville; Watmore, Akpom, Johnson
We say: Stoke City 0-1 Middlesbrough
Two strong sides face-off on Saturday, and there is not a lot to separate the two on paper. Lots of goals have been scored at the Bet365 so far this season, but Boro are a tough nut to crack and we see them coming away with the spoils - beating a fellow promotion rival for the second time in four days.