City will become the first English club to win four successive top-flight titles if they beat West Ham at the Etihad Stadium on Sunday (Monday AEST).
The reigning champions head into their final Premier League game of the season with a two-point cushion over Arsenal, who host Everton, and know their destiny in their own hands.
City manager Guardiola said: "I know they will be so focused. Everybody knows what we are playing for.
"It is something we will not live again, none of us, it's impossible - the chance to win four in a row. Not for any of us, in our lives, is it going to happen again.
"You have to live it, enjoy and think what you have to do during 95, 96, 97 minutes."
Victory would not only secure Guardiola's fourth title in a row but his sixth in the last seven years. He could then top off another outstanding campaign by becoming the first manager to win back-to-back domestic doubles in England next week.
Next season will be the last of his current contract and, until a decision is made about his future, speculation over his intentions will only increase. The one apparent certainty is that he has no intention of quitting this summer.
"I have a contract," he said. "I want to be here next season."
A theory has taken hold that rival clubs may have to settle for second best until Guardiola does decide to move on, but he insists he is not unbeatable.
The Spaniard said: "That's wrong. (Look at) the margins. If every season we won by 20 points I'd say yes, I'm a genius, I'm so good, but it's not (like that).
"The Premier Leagues we won against Liverpool, they could have won. Arsenal could win (now).
"My opinion on Liverpool - nothing changes if they win or don't win. I know just the winners are prized, they smell good, but it should not be the case.
"Before arriving here (at the last game), there's been a lot of work behind it. Like at Liverpool and Arsenal this season, there has been a lot of work. It's not because of what we have done in the past."
Guardiola will again put his faith in second-choice goalkeeper Stefan Ortega after number one Ederson was ruled out with the fractured eye socket suffered in the midweek win at Tottenham.
The German has come off the bench to take over from Ederson on four occasions this season and, after he made some critical saves to hold off Spurs, Guardiola has full trust.
He said: "Today, in modern football, you have to have two proper good keepers.
"Before it was clear (who) the first keeper and second keeper (were), the distance was so big.
"Of course everybody knows that Ederson is the first keeper but the distance is not big."
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