The reigning Premier League champions went down 1-0 to their domestic rivals in the first leg but welcome Mauricio Pochettino's men to the Etihad Stadium on Wednesday.
While former Arsenal and Germany defender Mertesacker is confident City can complete a comeback this week, he does not expect the same of their city rivals Manchester United, who trail Barcelona 1-0 ahead of Tuesday's game at Camp Nou.
"Does Pep still know how to succeed in the Champions League? Of course he does and City will progress," he told Goal. "When City play the second leg at home and the team have the feeling they have to make up for something, that's when they play best.
"Plus, Spurs always had big problems in Manchester and got some heavy defeats. I don't expect that now, but they will surely miss Harry Kane. City have the big goal to win the Champions League and I don't think Tottenham will spoil that. I actually believe the final will be Man City vs Barcelona."
The 34-year-old is also confident in Liverpool's ability to protect their 2-0 aggregate lead over Porto when they meet again in Portugal, but he believes Jurgen Klopp's team are too intense to stay in the fight with City for the Premier League crown.
"Liverpool and Klopp have a had a certain journey so far and that journey absolutely calls for success," he added. "They've had a fantastic season and have kept up with Man City – the best team in England.
"I count a lot on Liverpool in the Champions League, because in knockout matches they are always able to bring that intensity into their game. Also I am convinced of Klopp's skills as a motivator. He is able to make the players even more hungry in these matches.
"In the Premier League I'd rather go with City. Liverpool's intense style makes it problematic for me to see them fighting for the title until the end."
But the presence of five-time Ballon d'Or winner Cristiano Ronaldo could tip the scale in the Italian side's favour.
"I think there could be another surprise, but I expect the Ronaldo factor to be decisive in the end," he said. "Still, Juventus were not too experienced for Ajax.
"Ajax's calm way of playing can be very dangerous for Juve. Ajax definitely have a chance away from home and Juve know that. Real Madrid's exit is a good warning. I expect Juve to defend deep, while Ajax lacked some patience in the final third in the first match. They must improve in that area."