The Dutch midfielder, 23, fell awkwardly near the byline in the second half, briefly attempted to continue before collapsing, and was stretchered from the pitch. Footage shared on social media showed Wolves supporters directing abuse at Simons as he was wheeled along the touchline.
Simons posted a statement on Instagram on Sunday morning that laid bare the scale of his heartbreak.
"They say life can be cruel and today it feels that way. My season has come to an abrupt end and I'm just trying to process it. Honestly, I'm heartbroken. None of it makes sense.
"All I've wanted to do is fight for my team and now the ability to do that has been snatched away from me — along with the World Cup. Representing my country this summer — just gone. It'll take time to find peace with this, but I'll continue to be the best teammate I can be.
"I have no doubt that together we'll win this fight. I'll walk this path now, guided by faith, with strength, with resilience, with belief, as I count down the days to getting back out there."
Simons joined Tottenham from Paris Saint-Germain last summer for £51 million. He has contributed two goals and five assists across 28 Premier League appearances this season.
His absence is a significant blow both to Tottenham's survival fight — they remain two points from safety with four games remaining — and to the Netherlands at the World Cup. Ronald Koeman will need to rethink his attacking midfield options.