They play a different kind of football. It was his eighth goal in 11 matches this season, a record that was soon matched by Jesus when the striker tapped in from De Bruyne's cross. Forty-eight per cent of Napoli's attacks come down their left, highlighting Lorenzo Insigne's importance when cutting in from that side.
But they have so far been less successful in the Champions League, sitting third in their group with three points after defeat at the Etihad Stadium.
City and Napoli's only previous meeting came in the 2011-12 Champions League group stages.
"They are an extraordinary squad".
Gabriel Jesus, Raheem Sterling and Leroy Sane were outstanding on the night as they tore Napoli's backline apart.
RealSport have picked out three key battles that could decide the game.
But a frustrated De Bruyne, who had had just been booked for dissent, was unhappy at some of the decisions given by Spanish referee Antonio Lahoz and his assistants and wanted to confront the fourth official as he walked off. The little Italian is an exceptional wide forward who possesses wonderful technique and has great intelligence and movement.
That looming question could easily cause Guardiola and City to balk at the player's asking price.
The Partenopei were more in the contest in the second half, restricting City to just the one wayward Sane shot in the first 15 minutes following the restart. I say it all the time but we've got to keep going game by game.
Much of the defensive work against Insigne will be left to the responsibility of John Stones.
De Bruyne's agent has confirmed he will open talks with City over a lucrative new contract for his client, whom City boss Pep Guardiola hailed as "the best player in Europe bar one". "They play a bit in the same way as us, so it's sometimes difficult". "Everyone is playing at a high level".
Harry Winks is too raw to be trusted with tracking Isco or Asensio, while Eric Dier is arguably not energetic enough for such a frantic encounter at the Bernabeu.
The Naples club have not won the league since 1980 but are two points clear of nearest rivals Inter at the top.
Guardiola's side are now unbeatean in 18 games in all competitions, 14 of them wins, since the 2-1 loss to Arsenal in the FA Cup semifinals. If he's dead set on matching the Brazilian talisman's deal, he may need to find a new club.
Speaking ahead of Tuesday's game, Guardiola said City will remain focus despite their recent impressive run in the Premier League.
De Bruyne, City's star player this season from central midfield, struck the crossbar from long range and Jesus had a shot cleared off the line.
The Napoli boss, though, said City were deserving winners after their fast start to the game. However, he may have to show a more disciplined performance if he is not to leave Napoli exposed in defence.
The talented midfielder's agent, Patrick De Koster referenced the contracts of two players as potential comparisons for the deal De Bruyne will ask for.