The European champion will be the most high-profile side to miss the tournament in Qatar after slipping to a humiliating play-off defeat to North Macedonia in March.
Italy was also absent from Russia in 2018 following a play-off loss to Sweden, meaning its exile from football's most storied competition will stretch to a minimum of 12 years.
The Azzurri also suffered group-stage exits in 2010 and 2014, meaning their most recent FIFA World Cup knockout tie remains 2006's final victory over France.
Mancini, however, is determined to end Italy's World Cup woes when the tournament heads to the United States, Mexico and Canada in four years' time, and believes their failure to reach Qatar was unjust.
"Winning with the national team is the best thing there can be," he said.
"Giving Italians such joy is incredible, now we have to wait four years. We will aim to win the next World Cup in America.
"We are working, unfortunately we will suffer until December - the disappointment of not qualifying for the World Cup does not pass me.
"It was totally unfair, but the defeats must be faced. We did not deserve to stay out of the World Cup, but unfortunately, that's how it went."
Asked why he chose to continue as Italy coach following its play-off embarrassment, the former Manchester City boss said: "Honestly, I don't know, at that moment I just wanted to turn the page because it went badly.
"But winning the European Championship gives an incredible joy. Now we have to wait a few years and then we want to try for those emotions again."
Italy have since salvaged some pride by winning their Nations League group, finishing above Hungary, Germany and England to reach next year's finals.
And Mancini was keen to emphasise the difficulty of that achievement, saying: "It wasn't easy, the boys put everything in.
"England are a danger to win the World Cup, they have an incredible squad and Hungary are a very physical team."
Italy will contest friendlies against Albania and Austria when elite club football pauses for the FIFA World Cup in November.