Spurs had to wait until the last game of the group stages to book their place in the knockout stages last season, but it has been a completely different story in the competition this term.
After spending over £100million on seven new signings, Spurs have been able to successfully rotate their squad and, as a result, they have strolled to victory in all five of their matches.
A couple of years ago facing Anzhi would have been a daunting prospect, but the Russian side are now shorn of stars like Willian, Samuel Eto'o and Lassana Diarra after a radical cost-cutting venture by owner Suleiman Kerimov.
Now the Russian club are only able to bring 20 people - including staff - to London for the fixture, meaning Spurs are big favourites to make it six wins from six.
"Another win would be brilliant for us," Spurs manager Villas-Boas said.
"It would really complete a good group run; completely different to the one we had last year.
"It would be good to finish on 18 points. We are qualified and Anzhi are as well. They go on a two-month break now for their winter break, so all of this adds to special circumstances in a game.
"But we will try to motivate our players to focus on a win and achieve 18 points and go through the game without any injuries."
The Russian season is just over the halfway stage, but Anzhi are almost certain to be relegated.
The club lie bottom of the Russian Premier League having failed to win any of their opening 19 matches and they come to London with a threadbare squad thanks to several injuries.
Manager Gadzhi Gadzhiev said: "Many players will miss the match. That is why we have recruited four youth team players.
"Together with the coaches we've recruited 20 people.
"Mikhail Kerzhakov is out. Evegniy Pomazan is sick. Ali Gadzhibekov suffered a jaw injury and was concussed at the weekend.
"Karlen Mkrtchyan has a knee injury, Andrey Yeshchenko hasn't travelled.
"We have only one forward - Serder Serderov. Islamnur Abdulavov is still out and Lacina Traore is as well."
The injury situation is so grave that Anzhi are considering naming youth team coach Ruslan Agalarov among their substitutes.
Spurs, meanwhile, look set to give Angola-born youngster Laste Dombaxe his debut. Fellow youngsters Ryan Fredericks and Shaquile Coulthirst have also been included in the squad.
Danny Rose and Christian Eriksen are available after they overcame their respective toe and ankle injuries.