City recovered from twice falling behind to outgun the French league leaders 5-3 in the opening leg in Manchester, but Monaco's formidable attacking threat could still shatter the Premier League club's aspirations.
Under Manuel Pellegrini last season City reached the semifinals for the first time, losing to eventual champions Real Madrid 1-0 on aggregate, and De Bruyne is confident they can go further with Guardiola.
"I think we can reach the final, but of course the other teams will think the same and that doesn't make it easier," the Belgium international told Uefa.com
"It will be very tough against Monaco, they're doing extremely well at the moment, but we are very positive and if we beat them we are through to the quarterfinals.
"After that, the final isn't that far away," he added.
Guardiola has won all seven previous last-16 ties with Barcelona and Bayern Munich, but City's recent away form is mediocre at best with just one victory in their last six games in Europe.
"We'd like to go through, but we cannot forget the team we are going to play. Their attack is the best, by far," Guardiola said after City defeated Middlesbrough 2-0 on Saturday to reach the FA Cup semifinals.
"It will be tough but we’ll try to play our game and try to be one of the best eight teams in Europe."
Radamel Falcao, who scored twice at the Etihad Stadium, is set to return to the starting line-up on Wednesday after coming off the bench in Saturday's 2-1 win over Bordeaux that kept Monaco three points clear at the top.
Eighteen-year-old starlet Kylian Mbappe has scored nine goals in his last eight appearances, including the opener against Bordeaux, and will have a key role to play if Monaco are to continue their strong record in two-legged ties against English teams, having won four out of five times.
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Jamie Vardy's goal in Spain ensured Leicester City remain firmly in the hunt for a quarterfinal berth despite a 2-1 first-leg defeat at Sevilla.
The Foxes used a 10-day gap in the fixture list to hold a training camp in Dubai ahead of Tuesday's return leg at the King Power Stadium.
Craig Shakespeare has been named as the club's manager until the end of the season, and Austrian left-back Christian Fuchs said the trip to the Middle East was a welcome breather.
"It was an intense time over the last couple of weeks. It’s good to come down and work a little on team spirit. When you win two games, that’s the best medicine for team spirit," Fuchs told Leicester's in-house TV channel, with the Premier League champions coming off back-to-back 3-1 wins over Liverpool and Hull.
Fernando Torres is expected to return for Atletico Madrid for their second leg at home to Bayer Leverkusen after a sickening clash of heads in a 1-1 draw with Deportivo La Coruna 10 days ago.
Diego Simeone's side, runners-up twice in the past three seasons, hold a 4-2 advantage going into Wednesday's clash in Spain.
Captain Gabi and defender Filipe Luis are suspended for Atletico, while Tayfun Korkut is the new man in charge for Leverkusen after replacing Roger Schmidt last week.
Porto face a monumental challenge to overturn a 2-0 deficit away to 2015 finalists Juventus.
The Italian giants are unbeaten at home since August 2015 and extended their incredible 17-month winning league run in Serie A as Paulo Dybala scored a controversial last-gasp penalty in a 2-1 victory over AC Milan last Friday.
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