The Belgian star missed Wednesday's defeat to Barcelona after he was forced off the field during last weekend's win over Huddersfield.
And international boss Roberto Martinez has now confirmed that the 31-year-old faces a lengthy stint on the sidelines.
He said: "Jan Vertonghen might miss two Belgium camps. Bad news."
If he is out of action for six weeks, the defender will miss matches against Cardiff City, West Ham, Manchester City, Wolves and a Champions League clash with PSV Eindhoven.
Vertonghen had cemented his spot in Mauricio Pochettino's starting XI and he had played in all seven of their league games this season.
Spurs, who are fourth in the Premier League table, are amid an injury crisis after just seven top-flight games.
Mousa Dembele missed the Barcelona clash after he was also hauled off at half-time against the Terriers with an injury.
Dele Alli missed the Champions League tie with a hamstring issue and Christian Eriksen has been nursing a groin problem.
But Pochettino has insisted that his team will not use injuries as an excuse.
The 46-year-old said: "We have players with different injuries – it's not a pattern that happens from something specific.
"We are not victims, though. We must feel strong. Every player must feel they can win and achieve what we want."
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