Grealish, on loan from Manchester City, is likely to undergo surgery after suffering a stress fracture in Everton's 1-0 win against Aston Villa on January 18th.
"We believe he's probably going to need surgery, but that's still not absolutely confirmed, but it probably rules him out for the rest of the season," Everton manager David Moyes told reporters on Friday.
"It's really disappointing for the player, and for the club, and all of us here.
"He's such an important part, he's a big character, big experience for us. We'll miss him. He's done a lot of really good things for us."
Grealish's last England cap came against Finland in October 2024, but his impressive Everton form had catapulted him back into World Cup contention.
England boss Thomas Tuchel spoke with him after Everton's win at Manchester United in November.
But now he is unlikely to be fit in time for the tournament, which will be held in the United States, Canada and Mexico from June 11th.
Grealish had been thriving at Everton, with two goals and six assists in 20 Premier League appearances.
The 30-year-old appeared to be approaching peak form again after a disappointing period at City, during which time he fell out of favour with boss Pep Guardiola.
Asked if Grealish's injury would hinder his chances of joining Everton on a permanent basis, Moyes said it was "far too early" to discuss long-term plans for the former Aston Villa star.