Places at the Germany tournament next summer are at a premium with a number of teams, including Scotland and Finland, unexpectedly shooting straight to the top of competitive groups.
But even outside of the eight groups, there will be vendettas needing to be settled.
That case specifically refers to the hosts, who are instead set for a pair of high-profile friendlies due to their place at Euro 2024 already being booked.
Tensions are already high in Die Mannschaft's camp with a four-game winless streak off the back of a disastrous 2022 World Cup campaign.
Head coach Hansi Flick is under huge pressure to turn around the team's fortunes and he may be running out of time ahead of their home tournament.
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Last time out they failed to sell-out Schalke's VELTINS-Arena and were booed during a 2-0 defeat to Colombia, and things could well get worse at Wolfsburg's Volkswagen Arena next up.
Awaiting them on Friday will be Japan, a name that will send shivers down their spines.
Last time the pair faced was as recently as November in Qatar when Germany got a schooling by a number of players who feature in their very own Bundesliga.
Germany were utterly dominant in the Group E opener, but failed to capitalise on an Ilkay Gundogan penalty only for Japan to comeback and take the win in the final 15 minutes.
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The defeat sent them on their way to an early World Cup knockout.
Italy too will be having flashbacks to an unexpected defeat against a surprise side, when North Macedonia denied them a spot at the World Cup.
The reigning European champions had an extraordinary drop off after their Wembley heroics, managing four wins and four draws in qualifying for Qatar 2022.
That left them second in Group C behind Switzerland and facing a play-off to reach the winter tournament.
With Portugal in their draw, the talk was already about how one of the last two European champions and football giants would be out of the tournament when they faced off in their play-off final.
However, Italy didn't even make it there. Losing to North Macedonia in their play-off semi-final in Palermo, Aleksandar Trajkovski's stoppage time goal in a 1-0 win stunned Italy meaning they missed out on consecutive World Cups for the first time in their history.
Now with Roberto Mancini given the boot and reigning Serie A winner Luciano Spalletti brought in, Italy are looking for a jolt to the system against North Macedonia this time around.
Their squad still looks completely unrecognisable, but there's some hope a return to form for the rapid Federico Chiesa could be exploited by Spalletti's thrilling brand of attacking football, and it will need to be.
The Azzurri currently lie third, behind England and Ukraine, albeit with only two games played, but this North Macedonia test will be a tone setter for their hopes of making it out, and may kill off a few old demons.
A far more historic but just as momentous case of giant-killing will also be revisited this week when the Republic of Ireland host the Netherlands.
Tied on three points in Group B, both teams will be fighting for the runners-up spot behind France, currently occupied by Greece.
It will be the first competitive meeting between the teams in 22 years, with the last being a nadir for the Dutch.
Despite playing with ten men for the final half hour due to Gary Kelly's second yellow card, former Liverpool man Jason McAteer scored the only goal of the match shortly after that had Bono of U2 singing his praises.
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Taking down giants like Ruud van Nistelrooy, Patrick Kluivert and Jaap Stam, Ireland dumped the Netherlands out of qualifying for the 2002 World Cup before then winning their play-off tie against Iran to make the final tournament.
Despite being a traditional giant on the international stage, the Netherlands are known for wobbly patches throughout their tournament history, and with things again shaky under Ronald Koeman, revenge against Ireland could be the perfect ship-steadying exercise.