Walker turned an ankle at home on Monday, while Wanyama is struggling to shake off the knock to the neck he picked up during last week's FA Cup quarter-final win over Millwall.
If Walker misses out, Spurs would be without both their first-choice full-backs, as Danny Rose has been absent since sustaining a knee injury in the 0-0 draw at Sunderland on January 31.
Kieran Trippier would deputise for Walker if the England international does not recover while if Wanyama is missing, manager Mauricio Pochettino may be forced into a tactical switch.
The natural replacement for Wanyama alongside fit-again Mousa Dembele would be Eric Dier - but Dier has been part of Spurs' three-man defence in recent weeks.
If Dier moves into midfield, Pochettino may revert to a 4-2-3-1 formation - or use Kevin Wimmer in a back three and stick to 3-4-2-1.