The centre-back pulled out of the warm-up against Aston Villa on Sunday with an adductor issue and was replaced in the starting line-up by Kevin Danso.
Although Thomas Frank insisted it was not a serious problem, Romero did not train with the Spurs squad on Tuesday and has not travelled for his side's latest Champions League test.
"It's an adductor strain,” Frank said at his pre-match press conference. “We will assess it more this week before we confirm any timeframe."
Destiny Udogie will also miss the match and, unless he shifts players out of position, it means Frank has no choice but to start the same back four again.
”The latest is that he got that knee irritation after international duty,” the Spurs boss said.
“We are assessing and working very hard to get on top of it. We'll know more day by day."
There could be a reshuffle in midfield after the struggles against Villa. Lucas Bergvall and Pape Matar Sarr have both had limited involvement recently but would add some energy and drive to the middle of the pitch.
Further forward, Xavi Simons has not hit the heights expected of him at No10 and there could be a temptation for Frank to try something different and move him out to the left where he made his first Spurs appearances.
Mathys Tel has led the line in the last two matches, but he is not in Spurs' squad for the league phase of the Champions League and so Richarlison is expected to return to the starting line-up.