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Guardiola got his tactics spot on in the reverse fixture at Santiago Bernabeu, as Gabriel Jesus and Kevin de Bruyne scored late goals to earn the four-time Premier League champions a huge away victory.
Madrid won ten successive games to overhaul their arch-rivals and win a 34th Spanish title after returning from lockdown.
City will be missing star striker Sergio Aguero through injury in the second leg, but Realwill also be without a talisman with Sergio Ramos ineligible due to suspension.
Rooney can't see Madrid keeping the Blues at bay without their captain, and has predicted that Guardiola will mastermind another positive result which will take them one step closer to an elusive Champions League crown.
"City may never have a better chance to win the Champions League," the Manchester United legend wrote in his latest column for The Times. "Sergio Ramos is suspended which is a huge loss to the Real defence and I think City will score. Whether they are solid enough at the back themselves is my only question.
"Real will target their centre-halves and it's a worry that this season every other Premier League'Big Six' club beat City.This shows Guardiola's team can struggle to keep the best sides out."
Rooney says that although Zidane has proven in the past he is capable of inspiring European turnarounds, he cannot see City losing from such a strong position.
The Derby midfielder added: "I saw Zinedine Zidane do it in his first spell as Real coach when he played against Guardiola-style teams in big games, and it brought him successes.
"Yet my money is still on City. They don't have to chase the game. They don't have to score. They can even afford to lose 1-0 and go through, and in the first leg they surprised Madrid by sitting in themselves.