The 27-year-old Argentina international, who captains Spurs, missed the North London club's last four matches across all competitions after picking up the problem during the warm-up against Aston Villa on October 19th.
Italian left back Destiny Udogie and French forward Wilson Odobert have also recovered from their respective injuries and are available for selection.
Spurs are third in the Premier League standings with 17 points from nine matches, trailing leaders Arsenal by five. Frank's side lead ninth-placed Chelsea by three points.
"The positive is that Romero, Destiny and Wilson will all be available for the squad," Frank told reporters.
However, striker Dominic Solanke is not expected to be back before the international break. The 28-year-old England international is sidelined with an ankle issue, having had minor surgery last month.
"We're very aware of when we get Dom back, we hope - touch wood - we have him back and no setbacks, so we are very aware of doing it the right way," Frank added.
Spurs are looking to bounce back after a disappointing fourth-round League Cup exit at the hands of holders Newcastle United on Wednesday.
However, Spurs face a challenging task, having struggled against Chelsea in recent years, with just one win in their last 13 Premier League meetings.
Frank emphasised the importance of the home crowd in what promises to be an intense London derby.
"Home game against Chelsea under the floodlights is going to be unique and special. I'm really looking forward to it," the Dane said.
"We need the fans behind us. I know they give us everything, and the best clubs are all united together.
"That is the plan and the aim.... (It is) Maybe the best stadium in the world and definitely the best fans in the world, and we know the sound in that stadium can be insane."