The Premier League outfit have kept their hopes of qualification alive with dramatic back-to-back wins over PSV Eindhoven and Inter Milan, and they will reach the knockout stages on Tuesday if they can better the Italians' result at the San Siro.
But Barcelona have already wrapped up top spot in Group B and are also three points clear in La Liga after a 4-0 derby thrashing of Espanyol at the weekend.
"I am an optimist and if we want to achieve something important at the Camp Nou then we will have to be excellent both physically and tactically," said Pochettino.
"Barcelona have one of the best teams in the world. We must be very strong in every way in order to have a chance against Barca."
Pochettino saw his side tumble to a 4-2 loss in the reverse fixture at Wembley in October as Lionel Messi produced an individual masterclass.
But Saturday's 2-0 victory at Leicester saw Spurs stay third in the Premier League, only six points adrift of leaders Liverpool after a strong start to the season.
The Argentinian may have to give youngster Kyle Walker-Peters a full Champions League debut at right-back, with Kieran Trippier and Serge Aurier both serious injury doubts.
"Peters is an option to play," he said. "Being in a difficult stadium like the Camp Nou will help him and make him stronger. He could play tomorrow (Tuesday)."