Belgium defender Vertonghen has not played a minute since injuring his hamstring against Huddersfield Town two months ago, but was named among the substitutes for the Premier League win over Chelsea and is now likely to be thrust into the starting XI.
Foyth, a regular in recent fixtures, is ineligible after missing out on the 25-man squad chosen for the group stage in September, while Davinson Sanchez is battling a hamstring problem of his own.
Pochettino is adamant Vertonghen can seamlessly step in alongside Toby Alderweireld for the make-or-break encounter.
"Yes, that's why he was on the bench [against Chelsea]," the manager said. "My decision was to play with Foyth and Toby.
"Of course Jan is ready to play. He has been working so hard the last three, four weeks. He's an important player for the team like everyone."
Centre-back Foyth has largely impressed since breaking into the first-team fold, scoring the winner at Crystal Palace and helping to secure a 3-1 victory over Maurizio Sarri's men on Saturday.
The 20-year-old Argentine was a victim of the club having too many foreign players on the books when the initial squad was named, an error Pochettino regrets.
"I'm so disappointed from the beginning," he said.
"Not only Juan, but Georges-Kevin N'Koudou and Vincent Janssen are out of the squad for the Champions League and that's so painful.
"It's a mistake we made that at this level of football we cannot repeat again. For different reasons we need to find a solution."
Pochettino confirmed the fit-again Danny Rose, recently sidelined by a groin injury, is also free to face the Nerazzurri, who scored two late goals to win the reverse encounter 2-1.