Defeat to Bosnia & Herzegovina ended Italy's hopes of reaching the 2026 World Cup.
Gennaro Gattuso's men took the lead courtesy of Moise Kean, however, a red card for Alessandro Bastoni completely altered the complexion of the game.
The home side were well on top by the time Haris Tabaković got his nation back on level terms but, with no goals after that, the game drifted to penalties.
Francesco Pio Esposito and Bryan Cristante both failed to convert from 12 yards while Bosnia netted all four of their spot kicks.
Italy have now failed to qualify for a World Cup since being dumped out at the group stage in 2014.
Despite their recent struggles, Italy remain one of the great footballing nations, capturing football's most revered international prize on four different occasions.
First champions of the world in 1934, Gli Azzurri didn't have to wait too long to land their next title, going back-to-back to win the 1938 World Cup that was held in France.
The next 44 years were a little more tough, however, losing out to Brazil in the 1970 final before going onto complete their third win 1982 edition played Spain.
A dramatic penalty shoot-out victory over France saw Italy lift the World Cup for the last time in 2006 but, ever since that moment, they have failed to produce their best on the world stage.
Consecutive group stage eliminations in 2010 and 2014 were bitterly disappointing but no one could have predicted that the four-time winners would miss out on the next three editions of the tournament.
Football was left stunned when Italy failed to beat Sweden in a play-off ahead of the 2018 World Cup and Roberto Mancini described his side's failure to defeat North Macedonia prior to Qatar as "the biggest disappointment" of his managerial career.
Italian football fans will now have to wait until 2030 to make their World Cup return.
