James Maddison is expected to miss almost the entirety of the new Premier League season after suffering an anterior cruciate ligament injury.
The Spurs playmaker, who was forced off on a stretcher after suffering a nasty blow to the knee during Tottenham's pre-season clash with Newcastle last week, will now undergo surgery and begin his lengthy recovery.
Maddison, 28, suffered the injury during an innocuous challenge and Frank confirmed it was sustained to the same knee he had injured last season, a setback which saw him miss the Europa League final win against Manchester United.
He underwent several tests after arriving back in the UK, and the club's initial fears that he had damaged his cruciate ligament have been realised.
It presents a nightmare for new Spurs boss Thomas Frank, who will now be without the influential midfielder for large portions of the campaign.
A Spurs statement read: 'We can confirm that James Maddison will undergo surgery for a ruptured Anterior Cruciate Ligament (ACL) in his right knee.
'The 28-year-old midfielder suffered the injury during our pre-season friendly against Newcastle United on Sunday in Seoul.
'His surgery will take place in the coming days and, following that, James will then begin his rehabilitation with our medical team.
'Everyone at Tottenham Hotspur wishes James a full and speedy recovery. We will be supporting him every step of the way.'
Maddison collapsed to the pitch in agony after rupturing the ligament and his team-mates were visibly distressed while he received treatment from club physios. He was then taken away on a stretcher and had his head buried in his hands.
The England international is then said to have departed the stadium on crutches.
Recovery from the procedure will keep him on the treatment table for several months, but a definitive timeframe has not been confirmed by Spurs.
Frank revealed after the friendly draw with Newcastle that it was a 'bad injury', which cruelly came shortly after Maddison had returned to match fitness.
'I think sometimes life and football can be brutal, but also sometimes very beautiful,' said Frank. 'So I think it was brutal in what happened to Madders. It looks like a bad injury. Of course we don't know exactly the status on it. It didn't look good.'
The hammer blow could force Spurs to turn to the transfer market again, despite them already swooping for Mohammed Kudus from West Ham in a £55million deal.
Spurs also missed out on Nottingham Forest midfielder Morgan Gibbs-White despite seemingly triggering a release clause. Forest reacted furiously and threatened legal action - and a complaint to the Premier League - over an alleged illegal approach over the player.
Dejan Kulusevski has been ruled out for the start of the season, too, after undergoing knee surgery in May, leaving Frank desperate for creative options.
Maddison scored 12 goals in 45 appearances for Spurs last season, and a damning statistic has revealed just how much they struggle in his absence.
According to Opta, Spurs have won 51 per cent of their top-flight matches with Maddison in the side (24/47) over the past two seasons, compared to just 24 per cent (7/29) without him.