Pundit expects a comfortable win for Tottenham.
Merson believes the midweek Champions League victory over Borussia Dortmund will have removed the doubts over whether they could win at their temporary stadium.
Swansea City lost their last fixture against Newcastle and Merson believes they will struggle at Tottenham, and is predicting a 3-0 victory for the home team.
He said: "We have always said they [Tottenham] are a good team but they need to win a league game at Wembley. They looked a bit nervous against Burnley and the longer the game went on you thought Burnley could score.
"But they went to Everton and ripped them apart - that could have been any score. I don't see too many teams doing that at Goodison Park. I think they win this comfortably."
Tottenham striker Harry Kane is in tremendous form, demonstrated in midweek with a brace against Dortmund.
The reigning golden boot winner has a knack of going on a hot streak, while Spurs are also boosted with the presence of Swansea City's top scorer from last season, Fernando Llorente, who they signed on transfer deadline day.
Swansea bought back Wilfried Bony from Manchester City to replace him, but even so, the odds are firmly stacked in Tottenham's favour this weekend.