The Premier League leaders tackle the Bundesliga side in the Veltins-Arena where they will start as favourites.
United are attempting to reach their third final in four years and it leaves Ferguson with an unusual nervousness, which in itself emphasises how important this competition is to him.
"You always get apprehensive at this stage of the competition," Ferguson said. "Semi-finals are never easy.
"We had the same situation in 1999 when we played our semi-final against Juventus.
"There was an apprehension in our first game at home that we released in the second leg.
"When we played Barcelona in the first leg (three years ago) we got the result we wanted. But the last 20 minutes of the second leg were absolute agony."
United emerged victorious on that occasion, clinging on to a single Paul Scholes strike at the end as Lionel Messi threatened to rip a final place from their grasp.
It has gone down as one of the great Old Trafford nights.
However, against German opposition, there have been quite a few miserable ones too.
That stunning triumph over Bayern Munich at the Nou Camp has rather obscured the fact United have not beaten German opposition in a two-legged game during Ferguson's time at the club.
"There is no way Manchester United will be led into believing this is going to be easy," said Ferguson.
"Schalke have beaten every team at home in the Champions League this season, including Valencia and Inter Milan. If you just take that in isolation, it is good form.
"This is going to be a difficult game and we will treat it that way."
Schalke coach Ralf Rangnick is convinced his side's relative inexperience will make them more hungry and passionate to win.
In contrast to United, who will be featuring in their 12th last-four clash and hoping to make the final for a fifth time, Schalke have never graced this stage of club football's most prestigious tournament.
Of Rangnick's squad, only legendary Spain striker Raul knows what he is going into.
However, rather than view the position as a negative for his team's chances of reaching Wembley on May 28, the Schalke coach sees it as a pretty significant positive.
"Sir Alex Ferguson has more experience and has won many more trophies," he observed.
"Manchester United do have a very experienced team, on average three to four years older than ours.
"But maybe the fact we are more inexperienced means we are a really hungry team with more passion.
"It is something that makes this match all the more alluring for our team.
"Our players are in this position for the first time, with the exception of Raul, who might be there for the last time.
"We have to show what we can achieve and get the best out of it, so hopefully this will be a benefit for us."