Rose joins Harry Winks and Kyle Walker-Peters on the sidelines as a wounded Manchester City make the trip to Wembley looking to end a run of three straight defeats in all competitions.
Rose has only made 14 appearances in all competitions so far this season, missing the first two months of the campaign while recovering from a long-term knee problem.
He was later in and out of the side as he battled for a place with Ben Davies and looked to regain full match fitness.
But further knee trouble ruled Rose out again in January and the 90 minutes he managed against relegation threatened Stoke last weekend was only his second Premier League appearance of the calendar year.
Spurs go into the City game on Saturday evening having won six Premier League games in a row to all but guarantee a top four place and Champions League qualification for next season.
Mauricio Pochettino's side have not been beaten in the Premier League since losing to City in Manchester in December, a very impressive run of 14 games. Taking into account a string of FA Cup fixtures, Spurs haven't lost in 20 straight domestic games.
City come into the game at Wembley off the back of Champions League elimination at the hands of Liverpool. Their 2-1 defeat on Tuesday marked a second consecutive home loss after going down 3-2 against Manchester United last weekend and missing the chance to mathematically seal the Premier League title in record breaking early time.
They had earlier been humiliated by Liverpool at Anfield in a 3-0 scoreline.