The centre-back picked up his fifth Premier League booking of the season last weekend against Arsenal, when he was shown a yellow card in the second half for dissent.
Kevin Danso is therefore comes in as Spurs look to win at home in the Premier League for the first time since the opening weekend of the season.
With Romero out, Thomas Frank has opted for more ball-playing qualities in midfield and sees Archie Gray handed a rare league start.
The youngster shone against Paris Saint-Germain on Wednesday night and starts, alongside Joao Palhinha after he was rested in midweek.
Mohammed Kudus also returns to the starting lineup as Frank reverts to a 4-3-3 formation which means Lucas Bergvall is selected over Pape Matar Sarr.
In attack, Randal Kolo Muani and Richarlison both impressed in the Champions League and scored three goals between them.
Kolo Muani has been in better form and offers more of an all-round threat and keeps his place in the side, with Frank confirming he is fit to start again against Fulham.