Both teams made it past the first round of the competition during the last edition, but only of them will get to go through this time around.
Match preview
Stoke City secured their first league victory of the campaign by beating Blackpool City 2-0 at the Bet365 Stadium on Saturday afternoon.
Goals in either half from Harrison Clarke and Jacob Brown secured a well-deserved three points from Michael O'Neill's men in a largely one-sided affair.
Consequently, the Potters have moved up into the second half of the Championship table and are now level on points with Sheffield United in the race for the last playoff place.
Next up is a first-ever meeting against lower league opposition who will be looking to pull off an upset with their home fans behind them.
Having lost each of their last four outings on the road by a combined score of 8-1, Tuesday's visitors will be keen to turn things around away from home and get the job done here.
Morecambe's poor start to the new season continued following a 3-0 defeat against Peterborough at the Weston Homes Stadium on Saturday.
First-half goals from Joe Ward and Ben Thompson left Derek Adams's men with a mountain to climb before Hector Kyprianou put the final nail in the coffin in the second period.
With just one point on the board, the Shrimps are currently in the relegation zone of the League One standings and in need of an urgent pick-me-up.
Off the back of five straight home games without a win dating back to April, Tuesday's hosts have it all to do as they look to end their barren run on their own patch.
Morecambe form (all competitions):
Stoke City form (all competitions):
Team News
After seeing his team fail to score in four games on the bounce, Derek Adams could be tempted to make some alterations to his forward line for Tuesday's game.
Twenty-two-year-old Caleb Watts will be pushing for a start here having recently made his Morecambe debut since signing on loan from Southampton.
Harrison Clarke opened his Stoke City account with a lovely finish against Blackpool, and the midfielder will be looking to deliver the goods once again.
Dwight Gayle is expected to lead the line for the visitors alongside Jacob Brown, who found the back of the net in his first start of the campaign.
Morecambe possible starting lineup:
Ripley; Watts, Delaney, Rawson, Love; Gibson, Fane; Weir, Hunter, McLoughlin; Obika
Stoke City possible starting lineup:
Bursik; Taylor, Flint, Wilmot; Clarke, Baker, Laurent, Smallbone, Tymon; Gayle, Brown