The Belgian’s latest injury was revealed after medical tests on a hamstring injury and Inter said the striker on loan from Chelsea "will be re-evaluated in a few days."
The World Cup starts in less than three weeks in Qatar.
Lukaku, who is Belgium’s first-choice striker, has just returned after two months out with a hamstring injury. He came off the bench against Viktoria Plzen in the Champions League on Wednesday and Sampdoria in the Italian league on Saturday.
Elsewhere, Lukaku’s former Manchester United teammate Paul Pogba will miss the tournament.
Pogba underwent an operation on a keen problem in September but his agent said that, following a medical review, the midfielder would not yet return to the Juventus squad or join up with France for the Nov. 20-Dec. 18 World Cup.
"Following yesterday and today’s medical review in Torino and Pittsburgh, it is extremely painful to inform Paul Pogba will still need recovery time from his surgery," his agent Rafaela Pimenta said.
"For this reason, Paul will not be able to join Juventus squad before the World Cup break nor the French National Team in Qatar. If wishful thinking would change things, Paul would be playing tomorrow."
Additional reporting from AP and Reuters