Head coach Villas-Boas left White Hart Lane by mutual consent on Monday in the aftermath of Sunday's humiliating 5-0 home thrashing by Liverpool in the Premier League.
That defeat left the London club eight points behind top-flight leaders Arsenal, despite the Portuguese having spent heavily in the close-season.
Technical co-ordinator Tim Sherwood will take charge of first-team affairs, along with coaches Les Ferdinand and Chris Ramsey, when Spurs look to secure a place in the semi-finals of the League Cup with a victory over out-of-sorts West Ham.
The interim management trio will be hoping for a vast improvement from the dire display against Brendan Rodgers' side.
West Ham have already won once this season at White Hart Lane when Winston Reid, Ricardo Vaz Te and Ravel Morrison were on target in a surprise 3-0 Premier League triumph in October.
Spurs midfielder Paulinho will start a three-match ban after his red card against Liverpool, while Michael Dawson will miss out after picking up his fifth booking of the campaign in the same game.
Sandro also looks set to be sidelined after suffering a calf injury at the weekend, but Danny Rose (foot) and Vlad Chiriches (knee) could return.
A lack of goals has been a major problem for a West Ham side that are hovering perilously above the Premier League relegation zone.
Sam Allardyce's depleted side were fortunate to secure a point from a goalless draw against bottom-of-the-table Sunderland on Saturday, and he plans to field an experienced side at Tottenham.
"Now, we're in a position where we have to see what we've got available for Wednesday night but there won't be any young players in there that's for sure. But there will be players who haven't played as much in the first team," he said.
Kevin Nolan serves the second of a three-match ban, and West Ham have a lengthy injury list that includes the likes of Stewart Downing (leg wound), Reid (ankle), Andy Carroll (foot), Mladen Petric (calf), and Vaz Te (shoulder).
Alou Diarra, Joey O'Brien, Matt Taylor and Carlton Cole could all be drafted into Allardyce's starting line-up.
‘He instantly popped into our ratings as one of the best U21 midfielders in Europe. The impressive thing is Slot has made him into more of a no.6' Inside Ryan Gravenberch's transformation at Liverpool
‘I don’t think Liverpool would look at Ollie Watkins, a striker isn’t a pressing issue for them – it’s Arsenal who need one’ Former Reds star explains why his old club don’t need an out-and-out forward this summer
