The Russians were eight minutes away from securing their passage to the Round of 32 on December 3, but conceded two late goals to the Netherlands' NEC Nijmegen in a 2-1 home defeat. A win for Spartak would also have seen Tottenham join the Muscovites in the next round. The top three teams in the five-team group qualify.
Spartak's defeat made the situation a lot more complicated, however. Italy's Udinese, with nine points, are the only side to have already secured a place in the knockout stage. Tottenham only need a point or a one-goal defeat to go through. A two-goal victory would see the Russians through irrespective of other results. If that happens, and NEC win in Italy against Udinese, goal difference would separate the London club and NEC.
If both Spartak and NEC lose, then goal difference will decide which of the teams makes the last 32. Indeed, if both teams lose heavily, Croatia's Dynamo Zagreb, currently in last spot after playing all their games in the group, could even go through. Defeats for both Spartak and NEC would mean that a team will qualify for the play-off stages with one win and three defeats - a first in the UEFA Cup group stages.
Spartak finished eighth in the domestic league this season, and a place in the UEFA Cup play-off stages would prove some consolation for their fans.
"This is our last match of the season, and the English championship is right in the middle," Spartak striker Nikita Bazhenov told UEFA. "That doesn't mean anything though. Everything depends on us." The Russian season runs from March to November.
Russian international Roman Pavlyuchenko, who signed for Tottenham from Spartak in the summer, is ineligible for the match, as he played for the Moscow side in the Champions League qualifying rounds.
Tottenham will also be without striker and top scorer Darren Bent, who is suffering from tonsillitis.
The match kicks off at 7:45 p.m. local time (23:45 Moscow time) and will be shown live on Russia's Sport channel.
GROUP D (after 3 games)
Dynamo Zagreb -3 (4 games)