The 23-year-old suffered a hamstring injury playing for Argentina in last month’s World Cup qualifier against Brazil and a second scan showed he will not be fit to play before 2022.
He will miss at least 10 games between now and January 2, starting with Brentford at home on Thursday, with boss Antonio Conte unsure when he will be fit again.
Conte said: “The news is not positive, the injury is serious. It will take time before we see him again. Surely next year, we have to check his injury week by week, but the injury is serious.
“Now he is trying to recover but he needs a long time to recover. It is a pity because he is an important player for us, the injury is very serious.
“I don’t know, January, February. But for 2021 he has finished to play. We have to wait and recover well.”
Romero’s injury could force Spurs to act in the January transfer window, but Conte is playing it cool, insisting he has had no thoughts about what next season might entail.
When you take a job, you have to make your evaluations and you have to feel your sensation. And honestly I felt Tottenham was the right club to work and to bring my ideas and philosophy of football. For this reason, I accepted the job.
“Honestly when I decided to become Tottenham manager I didn’t speak about this aspect,” he said.
“When you take a job, you have to make your evaluations and you have to feel your sensation. And honestly I felt Tottenham was the right club to work and to bring my ideas and philosophy of football. For this reason, I accepted the job.
“I didn’t talk about January or the way to improve the team. I repeat: I’m here because I have great enthusiasm, great patience to start a new work with Tottenham.”
Romero’s Argentina team-mate Giovani Lo Celso, who also returned from international duty with an injury, will also not be fit for the London derby with the Bees.
“Giovani Lo Celso, like Cristian Romero, they were injured with the national team,” Conte said.
“For sure it was a pity but Giovani’s situation is much, much better than Romero.
“My expectation is to see him the day after we play against Brentford. He’s started to work on the pitch.
“For sure Giovani is another player we need to try to exploit. He’s a good player and now I want to work with him.”
Steven Bergwijn has been linked with a move away from the club in January, with reports in Holland suggesting Conte is not keen on the winger.
The Italian said he has to perform an “important evaluation” of the Dutchman but sees him as part of his squad.
“We’re talking about a player that has important skills and it was a pity for me – but not the national team, because he scored in qualifying for Holland – because I would have liked to have him during the two weeks on the international break to work with him and know him much better,” Conte added.
“But for sure he has great quality. He’s good one v one, he’s fast, he has quality, he can beat a man and also score. Now we’re working.
Surely he's a player that I have to make an important evaluation of. But he's in my squad and I count on him for sure.
Conte on Bergwijn
“Now also he’s understanding what I want from him. And for me, he’s one of the strikers who can play in all three positions of the strikers.
“Surely he’s a player that I have to make an important evaluation of. But he’s in my squad and I count on him for sure.
“(On Thursday) he’s ready and available. (Against) Mura, he had a problem, otherwise he would have played. But (against Brentford) he’s ready and available and I count on him.”