Arsenal will enter Saturday's clash at the Emirates Stadium four points and three positions behind their bitter rivals in the Premier League table.
The Gunners have already lost four league games this season, and Merson has suggested that a fifth could lead to Wenger, who signed a new two-year deal in the summer, assessing his future.
"If Tottenham win this by three or four I can't see any way back for Wenger. Forget about the FA Cup and winning that, if they get beat by three or four I think he could go 'that's it, I might as well leave'," Merson told Sky Sports News.
Arsenal have won all five of their home Premier League matches this season, while Tottenham have won four of their five on the road.