The Royals have recovered some form in their battle to stay in the Barclays Premier League, collecting 10 points out of a possible 15 since the start of the year.
That upturn in fortunes has been down in no small part to McDermott's men showing a never-say-die attitude which has seen them coming from 2-0 down with eight minutes left to beat West Brom 3-2, before then hitting two goals in the final three minutes to snatch a draw against Chelsea.
Although the Royals could not produce a repeat performance at Stoke last weekend, McDermott is confident his squad have the battling qualities to test United right through to the final whistle at Old Trafford.
"Since I have been manager, I have been lucky enough to get a lot of great wins, coming from behind, and we were really unfortunate not to be able to do it again last week," McDermott said on Reading Player.
"Obviously we don't want to concede, but if we do, we know this team will keep going to the end.
"While you can't rely on a late comeback, you know if you are in that situation, the players have that heart and desire to come back."
McDermott added: "This is the toughest game you can have, if we are going to get into the next round, we are going to have to do it the hard way.
"We played Crawley (in round three) and were under pressure to win that one at home, then were favourites against Sheffield United.
"We won't be favourites at Old Trafford, we know that, but it is just a fantastic opportunity for our players and we are looking forward to it."
McDermott accepts Reading were too much of a soft touch earlier in the season, when they looked set for a swift return to the npower Championship after seven defeats on the spin.
"We have changed more of the system and have found a way to win," he said.
"We played some fantastic games which were great to watch, we lost 7-5 against Arsenal, which was a tennis score, then 4-3 against Manchester United, 3-3 with Fulham, all great games to watch but they are only great games for us if we win.
"We had to stiffen things up and I have made us a bit more difficult to play against."
Reading used the extra preparation time to out for some warm-weather training in Dubai and McDermott believes it was a worthwhile trip.
"We wanted to go away and get some training in a different environment," he said.
"The weather has been fantastic and it is good for the boys."