Victory for Andre Villas-Boas' men, combined with a draw between Anzhi Makhachkala and Tromso, would guarantee Tottenham's progression from Group K after just three games.
Sporting, of Portugal, were the last team to secure qualification in such rapid fashion, doing so three seasons ago.
After scoring five goals without reply across their opening two group games, Tottenham will be fancied to maintain their 100 per cent record against an opponent with two draws to their name.
Jermain Defoe has been responsible for three of Spurs' group-stage goals and also scored twice in the second leg of the qualifying play-off with Dinamo Tbilisi.
Providing he starts, as anticipated, Defoe will be eager to continue his good form and stake a claim for more frequent action in the Premier League.
The 31-year-old also has the incentive of needing one goal to equal Martin Chivers' record for the most by a Tottenham player in European competition (22).
Villas-Boas is likely to make several changes to the team that recorded a 2-0 league victory over Aston Villa on Sunday.
Together with Defoe, Erik Lamela, Mousa Dembele and Christian Eriksen will be among those hoping to feature from the outset after being named as substitutes at the weekend.
There could also be a second start of the season for England international Aaron Lennon, who has recovered from a foot injury and came off the bench against Villa to make his first appearance since August.
Sheriff have displayed fine form in Moldova's top flight this season, though, winning nine out of 12 games to open up a four-point lead over nearest rivals Veris at the top of the table.
With Veris set to visit the Sheriff Stadium three days after Tottenham, it remains to be seen whether Veaceslav Rusnac will choose to rest players for the Europa League fixture.
Sheriff opened their Group K campaign with a 0-0 stalemate at home to Anzhi before drawing 1-1 with Tromso in Norway.
Luvannor Henrique boasts 11 goals from eight appearances this season, however, and can therefore be expected to provide Sheriff's chief threat on Thursday.