The League One rivals played out a 1-1 draw at Hillsborough in the first meeting, setting up a pivotal replay in Lancashire.
Match preview
When Fleetwood took the lead via Promise Omochere's 52nd-minute strike at Hillsborough, the visitors were on course to reach the fifth round of the FA Cup for the very first time, but they failed to see the job through.
Josh Earl scored an unfortunate own goal midway through the second half, and neither side managed to find a winner, although Sheffield Wednesday could - and probably should - have booked their place in the next round.
The Fisherman saw just 31% of the ball in the previous meeting, with the hosts dominating large spells of the game, but Wednesday managed a solitary attempt on target throughout the clash, despite racking up 15 shots.
Fleetwood suffered a 3-2 defeat to Burton Albion on Saturday, with Charlie Kirk netting the winner for the visitors deep into stoppage time, meaning Scott Brown's side have lost each of their last four league games.
As a result, Fleetwood find themselves just two points outside the relegation zone in the League One table, 32 points behind first-placed Sheffield Wednesday.
The Owls have only lost three of their 28 league matches this season, picking up 18 wins and seven draws along the way, and they also boast the best defensive record in the third tier, having conceded a measly 18 goals.
Darren Moore's side extended their winning streak in the league to six games with a 1-0 victory over Plymouth Argyle on Saturday, keeping their fifth successive clean sheet in the process.
When you look at the bigger picture, Wednesday have avoided defeat in each of their last 16 League One outings, and they are also enjoying a 14-game unbeaten run across all competitions.
After kicking off their FA Cup campaign with a 2-0 win against Morecambe, the Owls beat Mansfield Town before booking their place in the fourth round with a hugely impressive 2-1 victory over Champions League-chasing Newcastle United.
Moore's men will be disappointed to have wasted multiple opportunities to beat Fleetwood last time around, but they will be confident of sealing the deal on Tuesday, having dominated the previous meeting.
Fleetwood Town FA Cup form:
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D
Fleetwood Town form (all competitions):
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L
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L
Sheffield Wednesday FA Cup form:
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W
D
Sheffield Wednesday form (all competitions):
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W
D
W
Team News
Fleetwood remain without long-term injury absentee Darnell Johnson, meaning Aristote Nsiala and Corrie Ndaba should occupy the centre-back positions on Tuesday.
Josh Vela was sent off in Saturday's defeat to Burton, so Lewis Warrington is expected to feature in central midfield for the hosts.
After missing a handful of games due to injury, Barry Bannan is back in action for Sheffield Wednesday, and the influential captain will aim to enhance his tally of four goals and six assists on Tuesday.
Josh Windass has chalked up 11 goals and five assists in all competitions this season, while Michael Smith has bagged 10 goals and three assists, so they will lead the Owls' attack.
Fleetwood Town possible starting lineup:
Lynch; Johnston, Nsiala, Ndaba, Andrew; Warrington, Sarpong-Wiredu, Robertson; Marriott, Stockley, Macadam
Sheffield Wednesday possible starting lineup:
Dawson; Iorfa, Flint, Palmer; Paterson, Byers, Vaulks, Bannan, Johnson; Windass, Smith