Teesside-born Cattermole will lead out the Black Cats alongside his close friend and Boro captain Matthew Bates, with whom he came through the ranks at the Riverside Stadium and still keeps in close contact.
The former England Under-21 midfielder made his Middlesbrough debut as a 17-year-old, going on to play almost 100 times for the club, before a £3.5 million ($5.5m) move to Wigan in 2008.
He returned to the north-east 12 months later in a £5m transfer to the Stadium of Light.
Despite coming up against several familiar faces, Cattermole insists there will be no love lost as the near-neighbours battle for local bragging rights, and more importantly a place in the fifth round of a competition last won by the Wearside club in 1973, when they famously upset Leeds United in the Wembley final.
There will be divided loyalties for Cattermole's Middlesbrough-supporting family, and the 23-year-old said: "For me, this is the best tie of the fourth round.
"It's a massive game for the area, it's caught the imagination and everyone's talking about the game.
"I speak to Matty a lot because we're big mates. We spend a lot of time together and socialise together. We've known each other since we were kids, and have been close since then as we're from the same area."
Bates, 25, has shown amazing resilience to battle back from four career-threatening knee injuries, catching the eye of Premier League scouts as he leads Middlesbrough's double bid for cup glory and promotion back to the top flight from the Championship.
Cattermole added: "Everybody questioned whether he'd be back, and I think sometimes he even questioned it himself following the injuries he has had. To come back from four cruciate knee ligament tears is unheard of, unbelievable.
"He's been out for spells of up to a year and no-one can know what he's been through and to emerge from that, you can't praise him enough. It'll feel funny shaking his hand before the game, but it will be serious.
"It's funny when you're kids together and then suddenly he's walking out with Boro and I'm taking Sunderland out of the tunnel. It's something I never thought would happen."
Bates admits the hosts are strong favourites, but believes Boro could still spring a shock on their short trip to Wearside.
"We're under no illusions. We're going into the game as the outsiders and underdogs, but that's sometimes not a bad position to be in. We're confident we can spring a bit of a surprise," he said.
Nicklas Bendtner, the Danish forward, misses out for the hosts with a broken nose suffered in the recent Premier League victory over Swansea -- Sunderland's sixth win in nine games under new manager Martin O'Neill.
Julio Arca, Middlesbrough's former Sunderland player, is suspended along with Scottish midfielder Kevin Thomson, as manager Tony Mowbray deals with several key absences.
The influential Nicky Bailey and Merouane Zemmama are both absent for the Teesside club, who were FA Cup final losers to Chelsea in 1997.
"Whatever team I put out, I know they will all put in a shift for the team and have pride in the shirt," Mowbray insisted.