Both sides will be looking to bounce back from defeats at the weekend. Spurs fell victim to a late winner from West Brom at the Hawthorns on Saturday, whilst Newcastle lost 2-1 against Watford at Vicarage Road.
Newcastle have already secured a place in the Premier League next season, and only really have a place in the top half of the table as motivation.
However, Spurs have a lot more on the line heading into this fixture. After a disappointing run of form recently, the Lilywhites have not yet managed to confirm their place in the Champions League for next season, and therefore will be desperate the bag themselves three points and keep themselves in the driving seat for a top four finish.
Spurs have not enjoyed the visit of Newcastle over the last few years. The past three times that these two sides have faced off in London in the Premier League have ended in a loss for Tottenham.
However, Spurs have won three of their last four fixtures at St James' Park, including a 2-0 win in the north east earlier in the season.
Mauricio Pochettino's side did record a 4-0 home win over the Magpies in the FA Cup in 2015, but then the following season a relegated Newcastle won 5-1 over a third placed Spurs at St James' Park.
So, despite Spurs' superior league status, it has been swings and roundabouts over the past few years with these two sides.
Christian Eriksen vs. Jonjo Shelvey
Christian Eriksen has been a vital player for Spurs this season. The dynamic midfielder has scored ten goals and racked up 11 assists in the league this term.
The Denmark international pulls the string in the midfield for Spurs, and Newcastle's Jonjo Shelvey will be tasked with trying to keep the midfielder quiet on Wednesday night.
Eriksen's pin point precision and long range shots could cause many problems for Newcastle, therefore Shelvey will have to stick to the playmaker at all times if he wants to stop Eriksen from having an influence on the game.
Spurs could be without Belgian duo Jan Vertonghen and Mousa Dembele for the clash on Wednesday evening.
Vertonghen picked up a knock on his ankle during Spurs' trip to the Hawthorns on Saturday and, following his departure from the game, the defender is thought to be a doubt for this fixture. Dembele missed out on Saturday, also with an ankle problem, and may not quite be ready in time for the visit of Newcastle. Serge Aurier is currently sidelined with a tight hamstring.
Ben Davies, Eric Dier and Heung-min Son are all likely to return after missing out on Saturday, adding fresh legs to the side that had a frustrating afternoon in the west midlands.
Newcastle, meanwhile, will be without winger Christian Atsu, who has missed the last four fixtures with a knee injury. Ciaran Clark is also not thought to be fit, although he has not been a starter for the Magpies recently anyway.
Rafael Benitez isn't expected to make many changes to the Newcastle lineup that lost to Watford, with DeAndre Yedlin and Matt Ritchie likely to be the only two to appear in the starting XI that didn't start on Saturday.
Potential Tottenham Starting Lineup: Lloris; Trippier, Sanchez, Alderweireld, Davies; Dier, Wanyama; Son, Eriksen, Alli; Kane
Potential Newcastle Starting Lineup: Dubravka; Yedlin, Lascelles, Lejeune, Dummett; Ritchie, Diame, Shelvey, Kenedy; Perez, Gayle
Spurs came out on top on the reverse fixture in August, earning a 2-0 victory at St James' Park. However, Newcastle have a good record when it comes to playing Spurs in London, having won on their past three league visits.
Both sides are coming off of the back of defeats, but the three points are definitely far more important for the home side, and therefore they should be going into the fixture with a lot more motivation.
Spurs need to get back to winning ways to keep themselves in poll position for a top four finish. A win would take them ahead of Liverpool into third place and ensure that Chelsea stay behind them.
Although Newcastle will not lie down, and will be going to Wembley with the hope of taking something from the game, the talent and ability of a determined Spurs side could prove too much for Benitez's team.
Prediction: Tottenham 3-0 Newcastle