Marton Jol was sacked following a run of five consecutive defeats, with head coach Rene Meulensteen taking full control of the struggling first-team squad.
The 49-year-old was installed as head coach at Craven Cottage on November 13, but was handed full control of first-team affairs after Fulham parted company with fellow Dutchman Martin Jol on Sunday.
Jol - who also had a spell as Tottenham boss - paid the price for a poor start to the Premier League season, including losing their last five top-flight fixtures, with the club languishing in 18th place.
His last game in charge proved to be a 3-0 defeat at West Ham on Saturday, as second-half goals from Mohamed Diame, Carlton Cole and Joe Cole secured the points for Sam Allardyce's men.
Ahead of his debut, Meulensteen - who served as first-team coach under Sir Alex Ferguson at Manchester United - said he would use his experience to guide Fulham to safety, with the club looking to move away from the relegation zone.
"I know what is required at the top end of the Premier League. This is a different challenge with different pressure. This is making sure you realize the need to keep three teams below you," he told Sky Sports.
Striker Hugo Rodallega (groin) and Matthew Briggs (hernia) remain missing for Fulham, while Dimitar Berbatov (illness) and Brede Hangeland (leg) are doubtful.
Tottenham has endured a frustrating start to the campaign, with a lack of goals accounting for its indifferent performances so far.
The White Hart Lane outfit has scored just 11 times in the 13 Premier League matches this campaign, with only Sunderland and Crystal Palace notching on fewer occasions.
But Andre Villas-Boas will be pleased with a spirited 2-2 performance at home to Manchester United on Sunday, a result that quickly eradicated the memory of a 6-0 hammering at the hands of Manchester City on November 24.
Tottenham occupies ninth position in the league standings, but is just three points adrift of Liverpool in fourth.
It will be looking for revenge, having lost 1-0 to Fulham at White Hart Lane the last time the sides met in the Premier League in March, with a Berbatov strike settling the game on that occasion.
Christian Eriksen and Danny Rose are both absent with ankle injuries for Tottenham, while Emmanuel Adebayor is doubtful with a groin injury.