The 26-year-old defender was involved in the Netherlands’ 2-1 Nations League victory over Serbia on Sunday but is now unable to continue with the national team.
The Dutch federation confirmed on Wednesday that Van Hecke had left the squad and would return to his club for treatment.
Van Hecke had started both of the Netherlands’ Nations League matches during the international window, playing the full 90 minutes against Germany before also completing the victory in Serbia.
The injury therefore comes at an inconvenient time for Tottenham, who signed the centre-back from Brighton during the summer.
Van Hecke had been one of the first major additions of Roberto De Zerbi’s tenure in north London, having previously worked with the Tottenham manager at Brighton.
Tottenham announced the signing in June, with sporting director Johan Lange describing Van Hecke as a defender the club had tracked for several years.
The centre-back had established himself at Brighton before making the move to Spurs and had also become a regular member of the Netherlands squad.
His withdrawal means Tottenham will now assess the extent of the injury before determining when he can return to club action.
The Dutch federation has not indicated that a replacement will be called into the squad.
Van Hecke’s departure is also a setback for the Netherlands, who are working through their first international window under new head coach Xavi Hernández.
He had played a full part in the team's opening matches, helping them draw 1-1 with Germany before starting the win over Serbia.
The Netherlands secured a 2-1 victory in Belgrade through two goals from Mexx Meerdink, with Van Hecke completing the match at centre-back.
He has now returned to London rather than remaining with the national team for the next fixtures.
For Tottenham, the timing will be monitored closely. Van Hecke has quickly become part of the club’s defensive plans following his summer arrival, while the international break had already placed significant demands on the squad.
The priority now is determining the severity of the problem and how long the defender will be unavailable.
The Netherlands have not yet confirmed whether another player will be added to the squad to replace him.