While the Serie A side are aiming for a first quarter-final appearance in 24 years, the German champions have made that stage for three years straight and are ultimately targeting a seventh European crown.
Match preview
While their domestic campaign has hardly gone to plan, Lazio are back in the Champions League's elimination phase following an eventful journey through the group stage.
Last term's runners-up to Italian champions Napoli, the Biancocelesti now sit eighth in the Serie A standings, due to an underlying inconsistency: they only ended a three-match winless run with last week's victory at Cagliari and lie five points adrift of the top four.
The first game in that sequence was a humbling Supercoppa Italiana loss to Inter Milan, and head coach Maurizio Sarri had to be publicly assured his job was not in jeopardy by club president Claudio Lotito not long afterwards.
During the autumn, Lazio heavily relied on home advantage to see them through Group E, in which they finished second to Atletico Madrid but above both Feyenoord and Celtic, winning two and drawing one of three fixtures in Rome.
Goalkeeper Ivan Provedel's ludicrously improbable late equaliser against Atleti was surely the highlight, as Sarri's side secured the capital club's third appearance in the Champions League knockout rounds.
On both previous occasions, Lazio were immediately eliminated - by Valencia in 2000, and none other than Bayern Munich in 2021.
Three years ago, the German giants won both legs of the clubs' last-16 contest, crushing the Biancocelesti 4-1 at Stadio Olimpico and winning 2-1 in Bavaria. Simply staying in the tie after Wednesday's opener will therefore be Sarri's priority.
Unbeaten in a dozen Champions League games against Italian opposition, Bayern have also progressed from 11 of their 12 most recent last-16 ties, except when losing to eventual champions Liverpool four years ago.
Following an imperious stroll through Group A, where they finished top by eight points and won all but one game, the German giants are now focusing on reaching the latter stages again.
Thomas Tuchel's side made short work of Copenhagen, Galatasaray and Manchester United, and it must be remembered that he previously took Paris Saint-Germain to the 2020 final and guided Chelsea to the ultimate prize one year later.
However, his reign in Munich has not run as smoothly as Bayern's hierarchy would have liked, because Die Roten trail Bayer Leverkusen by five points in the Bundesliga following Saturday's 3-0 reverse to their irrepressible title rivals.
For once, free-scoring Harry Kane was unable to add to his towering goal tally at the BayArena, as Tuchel's team failed to spark in the final third and were well beaten by the side managed by ex-Bayern midfield maestro Xabi Alonso.
While Lazio are still in the Coppa Italia - they booked a place in the semi-finals by beating arch-rivals Roma last month - the six-time European champions have already exited the DFB-Pokal in embarrassing fashion and lost the DFL-Supercup to Leipzig.
The prospect of a trophyless season is particularly unpalatable for Die Rekordmeister, who see silverware as a right rather than a rare privilege, so there will be a certain amount of pressure on the shoulders of Kane and co.
Lazio Champions League form:
D
W
L
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L
Lazio form (all competitions):
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D
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W
Bayern Munich Champions League form:
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W
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D
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Bayern Munich form (all competitions):
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L
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L
Team News
As Nicolo Rovella returns from suspension, Maurizio Sarri must choose between the Juventus-owned midfielder, Danilo Cataldi and Matias Vecino to feature in Lazio's three-man engine room; the other two slots are set to be occupied by Matteo Guendouzi and Luis Alberto.
Spanish centre-back Patric is still struggling with a shoulder problem, but Mattia Zaccagni may be back in the Biancocelesti's squad after a toe injury.
Having scored his 200th Serie A goal at the weekend, captain Ciro Immobile will again lead an attacking triumvirate. The Italy striker averages a goal every 99 minutes in the Champions League, with only Simone Inzaghi netting more times for Lazio in Europe's top club competition.
Meanwhile, no player has been directly involved in more Champions League strikes this season than Bayern Munich's Harry Kane, who has four goals and three assists so far - only in 2017-18 has the England captain played a part in more.
Die Roten have added Sacha Boey, Eric Dier and Bryan Zaragoza to their options since the group stage, though the latter could be ruled out of Wednesday's game by illness.
Thomas Tuchel's list of absentees remains lengthy, as he cannot call upon Kingsley Coman (hamstring), Serge Gnabry (groin), Konrad Laimer (calf) and Bouna Sarr (knee), while Alphonso Davies is doubtful due to a muscular injury.
It remains to be seen whether the ex-PSG coach will revert to a four-man defence following Saturday's events in Leverkusen - that may see Dier dropped to the bench.
Lazio possible starting lineup:
Provedel; Marusic, Romagnoli, Gila, Hysaj; Guendouzi, Rovella, Alberto; Isaksen, Immobile, Anderson
Bayern Munich possible starting lineup:
Neuer; Mazraoui, Upamecano, Kim, Guerreiro; Kimmich, Goretzka; Sane, Muller, Musiala; Kane