Santo - as expected - made sweeping changes for Wednesday's EFL Cup win at Wolverhampton Wanderers, and the likes of Sergio Reguilon, Emerson Royal and Hugo Lloris will all return to the defence at the Emirates.
Eric Dier could displace one of Cristian Romero or Davinson Sanchez - neither of whom looked convincing at Molineux - for the derby, and the Colombia international may be the one to hold his place given his greater Premier League nous.
Tanguy Ndombele did bag the opener in midweek as he seeks to reignite his Tottenham career, but he is the most likely candidate to drop out for Pierre-Emile Hojbjerg as Oliver Skipp and Dele Alli retain their spots in the middle.
Lucas's return to fitness could see him earn a start on the right over highly-rated prospect Bryan Gil, while Son Heung-min has also returned at a crucial time to take his rightful place on the left flank.
Harry Kane has failed to fire in the Premier League so far this season, but his record of 11 North London derby goals is unparalleled, and the England captain will once again be out to silence the Emirates this weekend.
Tottenham possible starting lineup: Lloris; Emerson, Dier, Sanchez, Reguilon; Hojbjerg, Skipp, Alli; Lucas, Kane, Son
> Click here to see how Arsenal could line up for the derby body check tags ::