Walsall boss Dean Smith is likely to give one or two of his fringe players a long-awaited chance to shine in the midweek clash.
The Saddlers have remained unchanged for the previous four League One matches and the likes of Ashley Hemmings, Febian Brandy and Richard Taundry will be hoping for chance to show what they can do.
Wholesale changes are unlikely, however, with League Two high-fliers Vale having lost only one of their previous 10 games in all competitions and Walsall keen to enjoy a sustained cup run.
Adam Chambers (hamstring) and twin brother James (thigh) will again be monitored ahead of the clash as they aim to make their respective comebacks, while fellow lengthy absentee Jimmy Walker could potentially make the matchday 16 should he recover from a thigh injury.
Port Vale manager Micky Adams has taken the unusual step of naming his starting line-up more than 24 hours before Tuesday's clash.
Influential skipper Doug Loft (calf) and goalkeeper Chris Neal (groin strain) are set to miss the second-round tie through injury. And with suspensions looming, Adams has decided to make changes elsewhere.
Sam Johnson will make his debut in goal behind a back four of Adam Yates, John McCombe, Richard Duffy and Rob Taylor.
Jennison Myrie-Williams, Chris Shuker, Ryan Burge and Ashley Vincent are set to line up in midfield, with leading scorer Tom Pope and Ben Williamson up front. Gareth Owen, Louis Dodds, Ryan Lloyd, Kingsley James and Joe Davis will be on the bench.
"We have to make changes, either through injuries or players being very close to suspension. We make no apologies for that but we will still try and win the game," Adams told the club's official website. "I am announcing my team for the game nice and early so that people can decide for themselves whether or not they want to come to the game.
"As I said, there are a couple of unforced changes in there because of injuries, and I have decided to rest Sam Morsy and Clayton McDonald as they are both on four bookings and I really don't want to risk them in a game like that."