The teams shared a goalless draw in Belgrade on matchday one in Group E, but it has been a story of contrasting fortunes thereafter.
Back-to-back victories over Asteras Tripolis, thanks largely to England Under-21 striker Harry Kane taking his group goal tally to an impressive five, have placed Tottenham firmly in the driving seat.
Coach Mauricio Pochettino will be keen to secure their passage on Thursday at White Hart Lane, where they are unbeaten in 17 Europa League group matches, and leave nothing to chance in a tricky closing away trip to Besiktas.
Partizan have endured a miserable time in Europe since they last faced their north London opponents.
Sasa Markovic belatedly scored his club's solitary goal of the round robin phase 13 minutes from time at Besiktas last time out, by which point Marko Nikolic's men were on their way to a third consecutive defeat.
In fact, Patizan have not tasted victory in their past 16 UEFA club competition group stage games - drawing four and losing 12 since a 1-0 win over Shakhtar Donetsk five years ago
Nikolic is likely to be without midfielder Darko Brasanac through illness, while Tottenham defender Federico Fazio is suspended following a late red card in the 2-1 win over Asteras - goalkeeper Hugo Lloris returns having suffered a similar fate a game earlier.
Pochettino must also run the rule over a host of players listed as doubtful, including attacking midfielder Nacer Chadli (knee), Andros Townsend (ankle) and forwards Emmanuel Adebayor (back) and Roberto Soldado (knock).
Nevertheless, the Argentinian has been happy to give opportunities to his squad players throughout the European campaign - something that paid obvious dividends with Kane’s emergence, with the forward now a regular face domestically.
Left-back Ben Davies added a maiden Premier League start to six in the Europa League when Tottenham secured a dramatic 2-1 Premier League win over Hull City on Sunday and the close-season addition from Swansea City hopes to follow a similar path to that trodden by Kane.
"It's important for me," he told Tottenham's official website.
"I've waited a while and I'm delighted to have got there. Hopefully it's the first of many. I want to kick on from here."