The Royals have built a reputation as comeback specialists in recent weeks and McDermott believes they will display those qualities once again at Old Trafford if required.
"Since I have been manager, I have been lucky enough to get a lot of great wins, coming from behind," McDermott said.
"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."
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."