The Citizens beat Watford 6-0 in last season's final at Wembley and, having seen Liverpool crowned as Premier League champions this week, Pep Guardiola's men will be determined to lift the trophy again having already won the Carabao Cup in March, just before the country went into lockdown.
City returned from the enforced break with a 3-0 win against Arsenal and a 5-0 victory over Burnley, although they were beaten 2-1 by Chelsea on Thursday evening as their hopes of a third successive league title were officially ended.
And Bruce said: "It looks as if they're going to be runners up in the Premier League and they'll not like that.
"The one thing they have been over the years now is serial winners, whether it's the FA Cup or the League Cup - they seem to own that one! They're a very, very good side and we'll have to be our best.
"They'll treat the cups now as something to look forward to. They've got the Champions League and of course they've got the FA Cup, which they will, I'm sure, put their attention to."
The Magpies' head coach - whose team drew 2-2 with the Blues on Tyneside in the league in November - added: "I think the mindset has got to be the same whenever you play Man City - you know that you're going to have to be your best.
"They've got some of the best players in the world performing, and that's what makes them pretty formidable; especially the way they play.
"So whether it's FA Cup, whatever competition it's in, Man City these days are the real deal so we're going to have to be at our best. We managed to be somewhere close to it against them earlier in the season - let's hope we can reproduce that and see if we can pull off a shock."
In the league game, the Newcastle supporters made a huge difference as they helped United come from behind twice, but unfortunately fans will not be able to attend on Sunday.
The match will be broadcast live on BBC One. For the latest coronavirus guidance, please visit gov.uk/coronavirus.
"How great it would have been to be in front of a full St. James' Park in a cup tie. It'd have been terrific," admitted Bruce.
"There's no disputing that it's strange; it's obviously strange for you (journalists) even watching it, so it is, of course, different. But as I've said many times now, it's better than what we had before, because we had nothing.
"A lot of people have put a lot of work in to make sure we've got this far. There's no disputing that we'd love a packed St. James's Park, but it's not to be. So we've got a big game, a huge game - can we go and be at our best? And we're going to have to be, because they're a very good team who we're playing against."
Isaac Hayden and Matt Ritchie - who scored the winner from the penalty spot when Newcastle beat City on Gallowgate in January 2019 - both suffered muscle injuries in the second half of Wednesday's 1-1 draw with Aston Villa, and Bruce revealed that both would be assessed ahead of the weekend.
But in-form Saint-Maximin, who has scored twice in his last three games, seems certain to start and Bruce said: "At the minute, he's going to cause a problem for any defence if he stays well.
"So let's hope it's his big night. It's a big stage - let's hope he goes and performs."
