The winner after next week's return in the Netherlands will progress to the playoffs, leaving them just one step away from the competition's new-look group phase.
Match preview
After a decade of dominance, Red Bull Salzburg finally failed to win their domestic title last season, as a spirited Sturm Graz side prevailed in a close-fought race that came down to the final day.
As a result, head coach Gerhard Struber paid the price and was replaced by ex-Liverpool assistant Pep Lijnders, who returns to front-line management following a brief spell in charge of NEC Nijmegen six years ago.
The Dutchman's start to life in the top job has gone well, as Salzburg completed an unbeaten pre-season schedule, winning all but one game, and then progressed in the Austrian Cup with a 6-0 victory over Dornbirn.
Last Friday's 3-2 win at Grazer AK saw Die Roten Bullen take maximum points from their first Austrian Bundesliga match of the 2024-25 campaign, despite letting a two-goal lead slip during an eventful first half.
They now aim to move closer to a place in this season's revamped Champions League, a competition from which they were eliminated at the group stage last year, finishing fourth behind Real Sociedad, Benfica and Inter Milan.
While Salzburg boast a recent history of regular involvement in UEFA's top club competition, Twente are hoping to make it back to the big time after 14 years away.
Two years ago, the Enschede club finished fourth in the Eredivisie and qualified for the Europa Conference League - their first return to Europe in eight years - then after missing out on European qualification again, they bounced back strongly last term.
A nervy final-day victory over PEC Zwolle secured third place for the Tukkers, and they now need to get through just two knockout rounds in order to reach the Champions League.
Joseph Oosting's side have since seen captain Robin Propper sold to Rangers, but four draws and one win in pre-season show that they may remain a tough nut to crack.
With well-travelled striker Ricky van Wolfswinkel still spearheading an attack that averaged over two goals per game in the league last season, Twente will have real hope of upsetting their more experienced opponents on Tuesday.
Red Bull Salzburg form (all competitions):
L
W
W
W
W
W
FC Twente pre-season form:
Team News
As is often the case for a club that previously nurtured Erling Haaland, Sadio Mane and Dominik Szoboszlai among others, Salzburg have had to rebuild this summer, following the departures of Luka Sucic (to Real Sociedad) and Strahinja Pavlovic (AC Milan).
They still have another potential star in their midst, though, as Ivory Coast international Karim Konate scored 20 league goals in 29 appearances last season, and he should start up front on Tuesday.
Another hot prospect, midfielder Oscar Gloukh, only returned to training on Thursday following Israel's exit from the Olympics, so he may join injured trio Fernando (thigh), Takumu Kawamura (knee) and Alexander Schlager (knee) on the sidelines.
Meanwhile, Twente lost their skipper and defensive mainstay Robin Propper to Rangers earlier this summer, but former Netherlands Under-21 striker Sam Lammers has travelled the other way and will offer assistance to main marksman Ricky van Wolfswinkel.
Sem Steijn finished as the Tukkers' top scorer in the Eredivisie last season, and he is set to start in Austria; however, Czech midfielder Michal Sadilek is doubtful due to a shin injury.
Red Bull Salzburg possible starting lineup:
Blaswich; Dedic, Baidoo, Blank, Terzic; Diambou; Capaldo, Kjaergaard; Daghim, Konate, Nene
FC Twente possible starting lineup:
Unnerstall; Reeger, Hilgers, Bruns, Kuipers; Kjolo, Eiting; Rots, Steijn, Lammers; Van Wolfswinkel