The Italian coach said he would not be distracted by criticism of Romero, who left to continue his rehabilitation from a knee injury with Argentina's medical staff ahead of next month's World Cup despite Spurs sitting just two points above the Premier League drop zone.
"With me he showed always his desire to stay with us. He is injured. I'm not stupid," De Zerbi told reporters on Friday.
"I think he can't change nothing, if he is in the stadium or not. I have no time to lose energy by thinking other things. We have to be focused on the game. We have players good enough to achieve our target."
A draw with 12th-placed Everton will almost certainly be enough for Spurs to ensure survival, as the North London club have a far better goal difference than 18th-placed West Ham United.
"We have to play with blood, character and spirit because it is a final," said the 46-year-old, recalling Spurs' triumph in the Europa League last season under former manager Ange Postecoglou.
"They played a great final last season, and they won a trophy. Maybe there was a bonus. After tomorrow, there is not a trophy or a bonus, there is something more important, the future and the history of the club. The pride of the players and the dignity of every one of us," De Zerbi said.
Solanke back for Spurs
Spurs will be boosted on Sunday by the return of forward Dominic Solanke, after he missed nearly a month with a hamstring injury.
"Solanke is available. We have to decide if he starts or not," De Zerbi said.
Djed Spence, who suffered a broken jaw during Tuesday's loss to Chelsea, will also be available, the manager added.
"The pressure is good. It depends if you are able to think, to stay strong, stay positive... this type of game you can become better as a coach, a player and a man," he said.
"You can become better by going through the tough moments. If everything is good in life, you can improve, but not in this way."