Having endured a controversial birth following Wimbledon's relocation, the Dons have become an accepted part of the football landscape over the past few years.
They are familiar opponents in cup competitions for the Cobblers with the two sides having met in the JPT last season and also in this year's Capital One Cup, a game which the Dons won 2-1 at Sixfields.
MK manager Karl Robinson has confirmed his intention to make changes for the tie but told his club's official website: "I want to win. It’s a local derby and it’s our 500th game so it’s a landmark occasion for us all as a Football Club."
Aidy Boothroyd meanwhile has allowed David Artell to leave the club by mutual consent while also agreeing a permanent contract with fellow central defender Matt Heath.