England right-back Walker is unavailable after sustaining a foot injury in last week’s draw at Burnley – a match goalkeeper Lloris missed through a knee injury which continues to keep him sidelined.
Vertonghen (virus) is one of several doubts for the Premier League encounter at White Hart Lane, where Harry Kane again wears the captain’s armband.
Aston Villa boss Tim Sherwood is again set to be without a key trio for his first return to Spurs since being sacked last summer.
Alan Hutton (ankle), Ashley Westwood and Scott Sinclair (both hamstring) are expected to miss out along with Carles Gil (dead leg), but Aly Cissokho (groin) could return after training again this week.
Libor Kozak will not be considered as he regains fitness following 14 months out with a broken leg. The striker played 67 minutes in the under-21s’ 1-0 win over Wolves on Wednesday, his first game since suffering the injury in January 2014.