The Bundesliga champions have completed the league-and-cup double in both of the last two seasons and are well positioned to do so again this campaign.
Leverkusen's run to the last eight of the DFB-Pokal has been far from smooth. They needed extra time to overcome Kaiserslautern in the last round and penalties to avoid an upset to FC Magdeburg before that.
Their unpredictable cup performances are indicative of a season in which they have had to work hard for consistency. Bayer started the campaign off with five straight wins in all competitions, but only recorded back-to-back victories in the league once more prior to March.
Roger Schmidt's side are now building some momentum at the perfect time, having won their last five Bundesliga matches, most recently a 4-0 stroll over Hamburger SV, to pull within two points of third place and resurrect their Champions League qualifying hopes.
With eight points back to fifth-placed Schalke 04, Leverkusen look safe for another season in Europe's premier club competition, which they exited last month by virtue of a penalty-shootout defeat to Atletico Madrid.
In his debut campaign in charge, Schmidt would be pleased with a repeat of the club's fourth-place finish from 2013-14, and delighted if they are able to combine that with progress to the semi-finals of a competition that they have won only once in their history - 22 years ago.
Should they knock Bayern out, the cup would be wide open.
Recent form (all competitions): DWWLWW
Pep Guardiola was the most sought-after coach in the world when he took the Bayern hotseat in 2013, but still some people questioned if he would be able to to match the legacy left behind by his predecessor Jupp Heynckes.
Heynckes won a historic treble which included the Champions League in his last year in charge of the Munich giants. How could Guardiola surpass that achievement? Well, successive domestic doubles would be a good start.
Only mathematics stands between them and another league title following a run of seven wins in eight games which has kept nearest challengers Wolfsburg at arms length, and a ninth cup triumph this century is just three games away too.
The trip to rivals Borussia Dortmund on Saturday was one of the few banana skins left for them this campaign, but they sidestepped that courtesy of a Robert Lewandowski goal which sent them 10 points clear at the top.
Their path to this stage of the DKB-Pokal has been comfortable to say the least, with two-goal victories over Eintracht Braunschweig and Hamburg following a relative walkover against Preussen Munster in August.
Wednesday should not be an easy night's work for Guardiola's men, but victory would set them up nicely for a season's end which promises so much. The same time next week, they travel to Porto in the Champions League last eight.
Recent form (all competitions): WWWWLW
Bastian Schweinsteiger limped out of the victory over Dortmund on 58 minutes with an ankle problem and, although tests have revealed that he has only suffered bruising, he sat out training on Monday and is a major doubt.
He joins a star-studded injury list of Arjen Robben, Franck Ribery, David Alaba and Javi Martinez, but one positive for Bayern will be that captain Philipp Lahm survived his first start in five months at the Westfalenstadion.
Thiago Alcantara made his return from a year-long layoff, but is not yet thought to be in contention to start so Sebastian Rode is expected to come into a midfield which may include the attacking talents of Mario Gotze at the expense of a more defensive-minded colleague.
Leverkusen remain without Robbie Kruse and Roberto Hilbert, but otherwise Schmidt has a fully-fit squad to choose from. Son Heung-min was rested at the weekend and is in line for a recall, but Hakan Calhanoglu may have to settle for a place on the bench.
Leverkusen possible starting lineup:
Leno; Wendell, Papadopoulos, Jedvaj, Toprak; Bender, Rolfes, Castro, Bellarabi, Son; Kiessling
Bayern possible starting lineup:
Neuer; Rafinha, Dante, Boateng, Bernat; Lahm, Rode, Alonso; Gotze, Muller, Lewandowski
Head To Head
Leverkusen have lost just one of their last five encounters with Munich at the BayArena and beat them 4-2 in the DKB-Pokal in 2009.
Bayern got the better of things when the two sides clashed earlier this season, with Franck Ribery scoring the only goal of the game.
Although that was the sixth game in a row between the two teams in which neither has scored over two goals, they have gone 52 meetings without a goalless draw.
We say: Bayer Leverkusen 0-1 Bayern Munich
With Bayern without several of their best attacking options, this fixture could be cagier than normal. That would favour the team who is best defensively, and Munich have conceded fewer than half as many Bundesliga goals as Leverkusen this season.