Lucescu was in charge of Inter Milan when they met the Red Devils in the Champions League quarter-finals just over 14 years ago.
Sir Alex Ferguson's side emerged triumphant, before recording victories against Juventus and Bayern Munich to lift the trophy for the first time under the Scot, who stood down after 26 years in the job last summer.
The transition is proving to be anything but straightforward.
United have lost three of their opening six Premier League games, their worst start since 1989, and travel to Ukraine with Ferguson's successor David Moyes under huge pressure.
"I played against Manchester United 14 years ago," said Lucescu. "Then it was a machine for winning trophies.
"It was more of an English team then. Now it's more international, so it's quite difficult to compare these two teams."
A veteran of almost a decade's service at Shakhtar, 68-year-old Lucescu realises how much upheaval Ferguson's exit has caused at the Old Trafford outfit.
"Of course every coach needs some time to look at a new way," he said.
"There can always be some changes of philosophy and maybe that's why Manchester United are facing some difficulties in their championship.
"We have analysed their games and noted there are always some changes. Because of rotation the links between players are not very good.
"Turnover creates a lot of problems for them. In the Ukrainian championship we are not rotating the squad as much. Maybe that is why we have been more secure."
Compared to Moyes, who will be taking charge of his first Champions League away game, Lucescu has 108 matches in the competition behind him.
Not that he feels it will make much difference on Wednesday.
"Tomorrow is a Champions League game," he said.
"It's a whole different level of competition and we'll see a different Manchester United.
"Maybe it's more important not to lose points in the Champions League than the Premier League."
Moyes has confirmed Rio Ferdinand is among the players who have not flown to Ukraine ahead of the encounter but Robin Van Persie is expected to feature in the game.
Ferdinand has picked up a slight groin strain, although Moyes revealed the 34-year-old would have missed the trip anyway.
"Rio has a slight groin problem," said the Scot.
"It is nothing serious but I was never bringing him anyway."
Moyes also confirmed Anderson, Fabio and Wilfried Zaha were also missing from Tuesday's flight.
At the weekend, Moyes appeared to suggest his side were not contenders for this season's competition because they did not have enough world class players.
However, the Scot is adamant United - who reached the final as recently as 2011 - would be giving their all in a bid to reach Lisbon in May.
"Of course we'll try to win the Champions League," he said.
"That's part of the job at Manchester United and I'll do everything I can to try to make that happen."
Source: DSG
Source: DSG