Peterborough United host Leyton Orient in League One's other semi-final first leg earlier in the day, with the former aiming to return to the Championship at the first attempt and the latter striving to secure second-tier football for the first time since 1982.
Preston are determined to commemorate their favourite son Sir Tom Finney, who passed away in February, by securing a promotion-clinching victory at Wembley.
However, the maiden English champions have never won the play-offs in eight attempts, having lost in the semi-finals five times.
Simon Grayson's team are expected to be roared on by a sell-out crowd at Deepdale and have, in Joe Garner, a striker high on confidence.
The former Blackburn Rovers man has scored 18 goals in 31 league game this season and this week collected the Sir Tom Finney Trophy as the club's Player of the Year.
"Hopefully it will be a full house and the supporters can get right behind us," said Garner, who scored in the 3-3 draw with Rotherham at Deepdale in February. "We are confident. At home lately we have been scoring goals at will."
Rotherham lost just two of their last 22 games to charge to a fourth-place finish – a run indebted to midfielder Ben Pringle and 21-goal attacker Kieran Agard.
Furthermore, manager Steve Evans is esteemed for his record in knock-out matches, which including guiding then-non-League Crawley Town to the FA Cup fifth round, where they lost 1-0 away to Manchester United.
"We have a successful track record in cup football, which tells you we can get people up for one-off occasions," said Evans. "You have three games to win your club promotion and we have worked really, really hard to make sure we are fresh and ready."
Kevin Lisbie and Dave Mooney inspired Orient to third place in League One, 12 points above Peterborough, but manager Russell Slade insists London’s second-oldest club are the underdogs.
"There is no doubt about that because you've only got to look at the bookies and we're not given a chance," said Slade.
"They have an excellent play-off record and are an excellent side. Darren Ferguson's done a great job and they've already won one competition (Football League Trophy) this season and played at Wembley. We know it's going to be very, very tough."
Peterborough's hopes will rest heavily on Britt Assombalonga, a jet-heeled 21-year-old striker who has netted 23 goals in 40 league matches in 2013-14.
