The four-time winners of FIFA's showpiece event were left at home while the world's best teams competed in the Middle East.
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This was Gli Azzurri's second consecutive World Cup that they had failed to reach in a major fall from grace.
Especially when just over a year earlier, Roberto Mancini's men beat England on penalties to become European champions.
National teams are returning to action for the first time since the tournament and Italy face the Three Lions in the Euro 2024 qualifiers this week.
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So with Mancini's side back in the spotlight, talkSPORT.com takes a look back at how they failed to qualify.
Why weren't Italy at the World Cup?
Italy were placed into Group C in the World Cup European qualifiers and finished second behind Switzerland.
Mancini's side were unbeaten across the eight games but four draws cost them top spot.
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As a result, they were placed into a play-off against North Macedonia, but despite having 32 shots at goal, they lost 1-0 and were knocked out.
Portugal then beat North Macedonia in the play-off final to seal their place in Qatar.
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After missing out, now Arsenal midfielder Jorginho revealed his disappointment: "It hurts, it hurts so much.
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"We have always created and dominated matches, but we have not been able to finish teams off. It is not to blame anyone in particular, but it is the reality.
"I don't know why we haven't been able to do this, I am also involved in this, and it hurts me to think about it."
So despite earning the crown as the best team in Europe, Italy were not at the World Cup.
Now, many people would argue that winning the Euros should earn a team an automatic place at the following World Cup, but as it stands, that's not the case.
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This has baffled former Italian forward Roberto Baggio, who said: "Italy won the European Championship, I think it's shameful, it's madness that they are not given an automatic berth to the World Cup for that.
"Anyone can lose one game against anyone else on a bad day, but these lads deserve some sort of reward for what they achieved, don't they? If I had been in that squad, I would've struggled to accept it."
Maybe the rules will change and if so, Italy will be going all out for another European Championships title in 2024.
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Gli Azzuri begin their journey against England and they will be keen to put Gareth Southgate's side to the sword to prove they are still one of the world's best.
Although the Three Lions, who reached the quarter-finals of the Qatar World Cup, will be out for revenge after defeat in the Euro 2020 final.