Both teams came away empty-handed from their most recent encounters, and they will be aiming to get back to winning ways as soon as possible.
Match preview
Stoke City got their EFL Cup campaign off to a good start by seeing off the threat of West Bromwich Albion in a 2-1 win three Tuesdays ago.
Alex Neil's men took the lead via a stroke of luck as Joshua Griffiths turned the ball past his own goalkeeper, but Brandon Thomas-Asante levelled matters in the 64th minute, only for Andre Vidigal to grab a winner barely 60 seconds later.
However, the Potters have been beaten in two of their subsequent three league matches and have slipped down to ninth in the Championship table, three points adrift of the last playoff place.
Lying in store next is the challenge of an opposing outfit who have often been on the receiving end in this fixture, having won just one of the last eight encounters since 2008.
Off the back of three straight home wins by a combined score of 7-2, Tuesday's hosts are flying in front of their fans at the moment and will be expected to turn on the style once again.
Rotherham United edged out Morecambe on penalties in the EFL Cup maiden round when the teams faced off at the Aesseal New York Stadium on August 8.
Matt Taylor's men went behind to Michael Mellon's opener but managed to restore parity through Joshua Kayode, after which Fred Onyedinma kept his cool from the spot to convert the winning penalty.
However, that is the Millers' only win in five matches across all competitions this term, and they suffered a second consecutive league defeat on Saturday, slipping down to 21st in the Championship standings as a result.
Winless in their last 16 competitive involvements on the road, Tuesday's visitors have work to do in their quest to avoid another fruitless outing away from home.
Stoke City EFL Cup form:
W
Stoke City form (all competitions):
Rotherham United EFL Cup form:
W
Rotherham United form (all competitions):
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Team News
Rotherham United will have to cope with the absence of Grant Hall and Lee Peltier, who are currently nursing muscle and calf injuries respectively.
Shane Ferguson is without an appearance for the away side in three months due to a hernia problem, and he is joined on the treatment table by Jamie Lindsay.
Stoke City's Lewis Baker is unavailable for selection as he continues to nurse an injury which has kept him out of action since the final day of last season.
Emre Tezgel also misses out through injury, but 23-year-old Tyrese Campbell recently made his return from the sidelines following a second-half cameo last time out.
Stoke City possible starting lineup:
Travers; Stevens, Wilmot, McNally; Tymon, Johnson, Thompson, Laurent, Hoever; Campbell, Vidigal
Rotherham United possible starting lineup:
Johansson; Bramall, Blackett, Humphreys, Lembikisa; Rathbone, Tiehi, Cafu; Green, Hugill, Onyedinma