While Posh are focused on finishing in the top two, Vale's only aim is to avoid relegation.
Match preview
Capping a frenzied few minutes at the home of English football, Peterborough captain Harrison Burrows somehow scored with a deep looping cross as stoppage time commenced, helping his club claim the EFL Trophy with victory over Wycombe Wanderers on Sunday.
Posh's 2-1 success over their fellow League One outfit was owed to a late brace for Burrows, who netted either side of Wycombe's equaliser, and they were crowned winners of the competition for a second time, having previously triumphed in 2014.
Now, Darren Ferguson's side turn their attention back to league matters, and they occupy fourth spot in the table, sitting eight points behind second-placed Derby County, who have played two games more.
Automatic promotion remains a possibility, then, but the playoffs are Peterborough's likeliest route back to the second tier, in spite of some fine recent form.
They have won eight of their last 10 matches, including a 2-1 victory over Leyton Orient on Easter Monday, and with wins from each of their last four league games against Port Vale, maximum points will be their sole aim on Wednesday.
Indeed, Vale suffered that quartet of defeats to Posh without even scoring, following a 1-0 home loss in October's reverse fixture.
After their goalless draw with Wigan Athletic last time out, the Valiants sit 21st in the League One table, with just goal difference separating them from the drop zone despite an improved run of results.
Closest challengers Burton Albion have played one game more, though, so manager Darren Moore will be keen to take something home from his side's midweek trip to London Road.
Last week's visit to Northampton Town resulted in a 2-0 loss, and Port Vale have now been beaten six times in their last 10 away matches, meaning the odds will be stacked against them.
Having also won just one of their last seven away games against Peterborough - and none since 2016 - Vale must be wary of the tough task that lies ahead of them.
Peterborough United League One form:
W
W
W
L
L
W
Peterborough United form (all competitions):
W
W
L
L
W
W
Port Vale League One form:
D
L
W
W
L
D
Team News
While Peterborough winger Michael Olakigbe has been ruled out until May, James Dornelly recently returned from a toe injury and Jacob Wakeling is also available after being cup-tied on Sunday.
Goalkeeper Will Blackmore and midfielder Jeando Fuchs are still sidelined, but the hosts have several attacking options to choose from, including Ephron Mason-Clark, who will join Coventry City at the end of the season.
The latter is Posh's top scorer with 19 goals in all competitions, while midfielder Ben Garrity leads the way for their visitors, on 12.
Once again, Port Vale will be without Mitch Clark, Dan Gore and James Wilson, the latter of whom was recently ruled out for the rest of the season.
Uche Ikpeazu is now nearing match-fitness, but Ryan Loft and England Under-17s striker Baylee Dipepa are set to battle it out with Gavin Massey for selection up front.
Peterborough United possible starting lineup:
Steer; Katongo, Knight, Edwards, Burrows; Kyprianou, Collins; Poku, Randall, Mason-Clark; Jones
Port Vale possible starting lineup:
Ripley; Sang, Smith, Iacovitti; Plant, Ojo, Garrity, Chislett, Sharrock; Loft, Massey