This is also Spurs' penultimate game at their temporary home of Wembley before moving into their newly built ground in August.
The reverse fixture ended in a 2-0 victory for Spurs on the opening day of the Premier League season.
Goals from Ben Davies and Dele Alli secured the victory for Spurs against a ten-man Newcastle side, who had Jonjo Shelvey sent off in the second half.
Who will partner Victor Wanyama?
If Mauricio Pochettino, sticks to his tried and trusted formation of 4-2-3-1, then he will have to find a partner for Kenyan international Victor Wanyama.
Pochettino confirmed in his pre-match press conference that both Eric Dier and Moussa Dembele will miss the fixture with illness and injury respectively. The obvious solution is to play former Newcastle player Moussa Sissoko in the role, as he has done previously.
On the other hand, Sissoko is better when going forward rather than being known for his defensive capabilities.
There is a lack of solutions, as young England midfielder Harry Winks, has been declared to be injured for the last two games of the season, but is in a race against time to be fit for the Toulon Tournament at the end of the month.
Pochettino could play a three at the back like he did for the majority of the game at West Bromwich Albion on Saturday, which will mean that there is not a need for two defensive midfielders.
There is also the option of promoting a player from the U23 squad.
The best player to fit the spot is Oliver Skipp. The 17-year-old has played 33 times for Spurs' U23 and U18 sides respectively this season. Pochettino is the man to promote the young players when he feels they are ready and maybe he will give Skipp a chance.
Kane's shooting boots have gone missing
Since returning from injury, Harry Kane has struggled to get back to his best and has shown in his play. He has scored just three times in his seven appearances since coming back from injury and one of those included that ghost goal at Stoke City.
That sort of form is not of someone who is chasing the Golden Boot.
If Kane can still find his shooting he is in with a huge chance of securing that third Golden Boot as he is currently just four goals behind Mo Salah and the Egyptian only has one game left to play to add to his title.
Is a Champions League place slipping out of Spurs' grip
After beating Chelsea, on Easter Sunday, many pundits and fans considered the race for the top four, almost an open and shut case.
As Spurs fans will a test to, being 10 points clear of the team chasing them, doesn't always mean that they are secure, as back in 2012, Spurs were in a similar position, being so far in front of Arsenal and an FA Cup Semi-final to look forward to.
Fast forward to May and they went on a woeful run of form and a humiliating defeat at Wembley to Chelsea, they saw their gap disappear and as a result of Chelsea winning the Champions League, Spurs were left without Champions League football.
Spurs are looking to do their first league double over Newcastle since the 2004/05 season
Newcastle have won their last three visits Tottenham (2-1, 2-1, 1-0)
Spurs have only lost two home games in their last 36 matches. (28 wins 6 draws)
Newcastle have won 3 out of their last 10 away matches.