Traveling to face the defending champs and still stinging from a bitter defeat in the Wild Card round of the 2010 playoffs, the Saints have an opportunity to not only make a statement to a national audience, but to also secure an important leg-up in what might be a battle for home field advantage throughout the playoffs.
The Saints are forced to confront the realities of a revamped roster, and they must make the immediate, necessary adjustments in order to emerge victorious in Week 1.
As preparations wind down and they get set to travel, here are four pressing issues facing the Saints, 36 hours prior to kickoff.
With newly-minted starting tackle Zach Strief set to man the right tackle position and returning left tackle Jermon Bushrod, the Saints' tackles will have their hands full dealing with the dynamic pass-rushing presence of Clay Matthews.
Fresh off of a 13.5-sack season, Matthews is a lightning-fast, disruptive force with the ability to single-handedly alter the outcome of a game.
Strief and Bushrod will have the vital task of neutralizing Matthews and allowing Brees time to operate in the pocket.
Brees is arguably the league's most deadly QB when he has time to throw, so keeping Matthews away from him is crucial if the Saints intend on winning this game.
Expect to see Matthews line up on both sides of the ball and the Saints to respond by either double-teaming or chipping him at the point of attack.
Saints WR Lance Moore missed practice both Monday and Tuesday with an ailing groin and looks unlikely to suit up for the Saints.
Moore is a key weapon in the Saints' attack, and his presence will be sorely missed if he can't go.
Last season, Moore ranked as the third-most efficient WR in the league according, to Advanced NFL Stats, and he consistently ranks as Brees' favorite target in clutch moments.
Moore's excellent hands, precise route-running ability and elusiveness rate him as one of the top slot receivers in the league.
Without Moore's presence in the slot, the Saints will be forced to adjust accordingly.
Look for Darren Sproles to absorb Moore's short yardage touches, Jimmy Graham to become the focal point in the middle of the field and Adrian Arrington to finally ply his wares in a big game.
Running the ball consistently and effectively is perhaps the Saints' top offensive priority heading into the game.
To do so, the Saints offensive line will have to handle the Packers' massive nose tackle, B.J. Raji.
The task of defending Raji will fall mostly on the shoulders of newly-acquired Saints' center Olin Kreutz.
Having faced Raji several times as a divisional opponent during his time with the Bears, Kreutz should be familiar with and prepared for the task at hand.
Double-teaming Raji with Kreutz and either of the Saints' All-Pro guards (Jahri Evans, Carl Nicks) gives the Saints an excellent shot at neutralizing Raji and establishing a sound running attack.
The Saints' biggest area of weakness on defense in 2010 was pressuring and sacking the opponent's QB.
Pressuring Aaron Rodgers on Thursday is of utmost importance if the Saints plan to slow down the Packers' attack.
The Saints ranked in the bottom half of the league in sacks in 2010 (33) and failed to generate consistent pressure, even in light of being one of the most blitz-centric defenses in the league.
In the offseason, the Saints drafted DE Cam Jordan with their first selection in the draft and added DT Shaun Rogers to improve the pass rush.
With Will Smith missing the game due to suspension, the Saints will start Jordan at one DE spot and free-agent signing Turk McBride opposite him.
Second-year pro Junior Galette will also see time at DE on pass-rushing downs.
If the Saints fail to generate pressure from the D-line early on, expect to see a variety of safety and corner blitzes to compensate.