With Pompey sat just inside the play-off places and a mere six games remaining, there is plenty to play for.
Danny Cowley’s men will be hoping to get enough points on the board to extend their campaign by at least two more matches.
Meanwhile, it is almost certain that their opponents on Saturday (12.30pm kick-off) will be playing League One football again next term.
MK Dons are safe from the drop in 14th spot and, barring an unlikely set of results, not going to climb into the top six.
But that represents progress for the men from Buckinghamshire, who were in the drop zone when Russell Martin replaced Paul Tisdale as manager a few months into last season.
Like the Blues, they recently enjoyed a four-match winning run, but have collected a solitary point from the past three games.
They were most recently in action on Tuesday evening, suffering a 4-0 defeat at promotion-chasing Lincoln.
Pompey were beaten 3-1 at Stadium MK last term, but goals from Tom Naylor and Ellis Harrison secured a 2-1 triumph when the sides met at Fratton Park back in October.
Alex Bass (foot), Lee Brown (hamstring), Ellis Harrison (knee), Jordy Hiwula (ankle) and Michael Jacobs (knee) are all still sidelined.
MK Dons defender Warren O’Hora is expected to miss the final weeks of the season with a foot injury, while Cameron Jerome and Louis Thompson are also unlikely to feature on Saturday.
HEAD TO HEAD
Pompey: 4 wins
MK Dons: 1 win
At Stadium MK
Pompey: 1 win
MK Dons: 1 win
Referee: Martin Coy
Assistants: Nicholas Cooper and Stephen Finch
Fourth Official: Scott Williams
Supporters in the UK can watch the action live – with graphics, commentary and replays – by purchasing a match pass for £10.
Please note that subscribers based in the UK and Ireland will still need to purchase a match pass in order to watch the game live.
There will be post-match reaction on the website and our official YouTube channel, with highlights to follow on Sunday.
ALSO IN LEAGUE ONE
Games kick-off at 12.30pm unless stated
Peterborough v Northampton (7.45pm)
Blackpool v Sunderland
Bristol Rovers v Lincoln
Burton v Plymouth
Charlton v Ipswich
Hull v Fleetwood
Rochdale v Accrington
Shrewsbury v Doncaster
Wigan v Crewe
AFC Wimbledon v Swindon (5.30pm)
Oxford v Gillingham (5.30pm)