United face Serie A leaders AC Milan in front of a capacity 80,000 at the San Siro needing to overhaul the Italians' single goal first-leg advantage if they are to advance to the Champions League quarter-finals.
As a challenge, Ferguson rates it even tougher than the mountain his team climbed to beat Juventus in the 1999 semi, after finding themselves 2-0 down at the Stadio delle Alpi.
But the Scot claims the current United vintage is better than the one which completed that stunning comeback - only Roy Keane will be part of both starting line-ups now Gary Neville has been ruled out - and in Van Nistelrooy, the Red Devils have the best striker in Europe at their disposal.
The prolific Dutchman uncharacteristically failed to covert two gilt-edged chances in the goalless draw at Crystal Palace on Saturday, failures that appear to have ended United's title aspirations.
Ferguson put those misses down to nothing more than ring-rust as the 27-year-old battles back to full fitness after four months on the sidelines with an Achilles injury.
And, with 36 goals in 38 previous European appearances for the Premiership outfit, Ferguson expressed the desire for Van Nistelrooy to be presented with the same chances he spurned at Selhurst Park. Because he is convinced this time, he will not miss.
"Hopefully Ruud will get the same chances he got on Saturday because there is no-one better at taking them," said Ferguson.
"Having the extra games will help him physically in terms of endurance and also on the mental side. In those aspects he is fine. The only issue is he does need games."
Van Nistelrooy actually rates himself as being in better shape than he was when he returned from a hernia operation against Lyon in September, when he scored twice to complete another memorable United comeback.
He acknowledged his physical state does not mean he is guaranteed to evade the clutches of fellow countryman Jaap Stam, who will start against his former club tonight, but he did admit a scoring contribution to a victory would be his biggest achievement since completing his £18.5million move from PSV Eindhoven in 2001.
"All the goals I have scored are in the past," he said.
"My career is all about what I produce now and this is definitely one of those occasions where scoring would represent my best goal."
Van Nistelrooy, along with talented youngsters Cristiano Ronaldo and Wayne Rooney, is the major reason why Ferguson rates this side better than the one containing David Beckham, Andy Cole and Dwight Yorke - a side that strode to the unprecedented Treble success six years ago.
"It is hard to look at those - Ruud, Cristiano and Wayne - and compare them with anyone. That is what sways it for me," enthused Ferguson.
Taking into account Gary Neville is missing this time, Paul Scholes came off the bench and Ryan Giggs was injured, Keane is the only constant from that amazing night in Turin.
Meanwhile AC Milan coach Carlo Ancelotti has warned his charges against complacency.
"We cannot think of the first leg result. We cannot prepare for this game focusing on the result we achieved at Old Trafford," he said.
However, Ancelotti believes a similar performance to the one they produced two weeks ago should be enough.
He added: "We have to go out on the pitch with the belief that we can repeat our display at Old Trafford.
"In terms of tactical play and how we interpreted the game, in Manchester we saw the best Milan.
Milan, joint leaders of Serie A alongside Juventus, have enjoyed their share of good fortune in recent weeks with late goals against Atalanta, Lazio and Cagliari.
But Ancelotti is unconcerned at being labelled as a lucky manager.
"The press can continue to say that I am fortunate, I am not offended," he added.
Ancelotti is set to play the same 4-3-2-1 formation he deployed at Old Trafford, with Jaap Stam likely to partner Alessandro Nesta in central defence and captain Paolo Maldini moving to left-back with Cafu or Kakha Kaladze, who is struggling with an injury making way.