The Royals travel to Old Trafford for Monday night's televised FA Cup fifth-round tie hoping to ambush United's attempt to repeat their treble success of 1999.
A midweek draw at Real Madrid has seen them put one foot in the quarter-finals of the Champions League and they sit a seemingly unassailable 12 points clear in the Barclays Premier League title race.
The business end of the campaign has brought with it a heavy and high-profile workload, but McDermott insists United have the resources to cope.
"Sir Alex Ferguson has talked about making changes against us, but the players that he can bring in are top, top players. We know that," he said.
"He's said his squad now is better than the one that won the 1999 Champions League and he'd know that. If he says they're better, they're better.
"They've been winning cups and leagues for years. They're used to the situation they find themselves in now.
"We watched the Real Madrid game the other night as a staff. That's football at the top level - full of fantastic players and great to watch."
Reading's Premier League outlook has improved since accumulating 10 points in their last five games, but they remain in the relegation zone.
The league remains their overwhelming priority, but McDermott refuses to view the FA Cup as an irrelevance.
"You're never in the situation where you can have a go at anything. You just pick your next game and do the best you possibly can in that match," he said.
"I don't prioritise any competition. It's our next game and we want to do the best we can against Manchester United in the FA Cup.
"We have to get the details right against United. The decisions have to go our way and we need to play well and defend well.
"If all those things come together then we have a chance of getting a result.
"We've got the chance to play Manchester United in the FA Cup with both teams wanting to reach the quarter-finals. It's a great occasion and we can't wait for it."
Reading returned from a four-day warm weather training camp in Dubai on Thursday and McDermott felt it was a productive trip.
"It was the right thing for us to do because the conditions over here last week were difficult to say the least," he said.
"We trained in 25 degrees heat and needed to get the best possible preparation for the next game.
"It was a good break for everyone and the squad's come back looking forward to the next game."