In 2021, Rotherham United have tended to favour a 3-5-2 formation which manager Warne thinks brings the best out of his side.
But without Harding and Mattock, who has been filling in on the left-hand side of a back three, and with Richard Wood struggling to play twice a week, he might not have enough central defenders to play it. Pulling players into the heart of defence could cause problems elsewhere.
Speaking before Monday's training session, Warne said: "As I speak to you now the players aren't in but I don't think Joe will be in any consideration for tomorrow night."
The left-sided defender came off in Saturday's 1-1 draw with Crewe Alexandra complaining of an Achilles problem. Harding was sent off for a second yellow card late in the game, and will therefore be suspended.
Wood has started every Saturday game this season, but his only Tuesday appearance was as a half-time substitute against Morecambe.
"We're stretched, but that's all part and parcel of the squad," said Warne. "We might have to play a different system.
"We all love Joe here, he's been a great performer for us and I think left-sided centre-back in a three is the best position for us.
"It does give you balance a left footer on the left side but if you need a back three the wide ones to be able to step in, to be able to play.
"Joe gives us left-sided balance so it's disappointing to lose Joe but people might just have to kick with their other foot.
"We'll come up with a solution to take on Wimbledon the best we can."
Wing-back Mickel Miller is unlikely to feature either.
"I don't see that, unfortunately," said Warne. "He might be available to train but he won't be available to start the game. If there's any risk there's no point me playing him but I was led to believe he won't be available for Tuesday."