Schalke consider themselves a total underdog against the three-time champions. But the Bundesliga team was also the outsider against Inter and still went through 7-3 on aggregate.
"Manchester United is a household name, just like Inter Milan before," Schalke midfielder Alexander Baumjohann said. "It's a dream of every player to be facing the Reds in a Champions League semi-final.
Both teams rested some of their top players over the weekend. United still won, 1-0 over Everton, but Schalke lost 1-0 at home to Kaiserslautern.
While United is closing in on the Premier League title, Schalke has nothing to play for in the Bundesliga, where it is stuck in the middle of the table.
Schalke has managed to reach the semi-finals despite a turbulent few weeks which included the sacking of coach Felix Magath, who was replaced by Ralf Rangnick.
The club was also shaken last week by the decision of goalkeeper and captain Manuel Neuer not to extend his contract, which still has another season to run. The Germany goalkeeper has not said where he plans to continue his career, but many believe he will leave for Bayern Munich in the off-season.
The defeat by Kaiserslautern was Schalke's first under Rangnick, with the players seeming to be more focussed on the Champions League semi-finals.
Influential defender Benedikt Hoewedes missed the game through injury and is in a race against time to avoid joining Dutch striker Klaas-Jan Huntelaar on the sidelines.
Raul Gonzalez, the Champions League's top scorer with 71 goals, won the competition three times with Real Madrid and could help set up a meeting with his former club in the final.
"We dream of beating United. Let's see if we're the better team," he told British newspaper The Guardian. "No one can believe this. A final would be even more incredible. I hope it's Madrid."
United captain Nemanja Vidic and midfielder Park Ji-sung were rested in Saturday's win over Everton and should return to the side. Michael Carrick, Ryan Giggs and Patrice Evra were among the substitutes at Old Trafford — the latter two coming on in the second half — and should also be back in the starting lineup.
Striker Dimitar Berbatov was ruled out on Monday after failing to recover from a groin injury and although Darren Fletcher is back in training after seven weeks out with a virus, the Scotland midfielder didn't make manager Alex Ferguson's 23-man squad.
"I enjoy this critical stage of a season when we are involved in big games that come thick and fast and I think we will be ok," Ferguson said.
Vidic said his team was the favourite, but then added that counted for little.
"Schalke scored five goals away from home against Inter. You have to respect that. Any team you play at this stage of the competition is not going to be easy," he said.