Portugal, the 2016 European champions, face Turkey in a play-off semi-final in March before a potential final against Italy, the team that succeeded them last year as kings of the continent.
“It would be very sad if we did not reach our objective, which is the World Cup,” the five-time Ballon d’Or winner told ESPN Brasil.
Ronaldo has not missed a major international tournament since making his debut for Portugal in 2003.
He has played in four World Cups and five Euros, also reaching the final in 2004.
“In football and in life we go through difficult moments but what matters is the ability to get back up,” the 36-year-old said.
“We know we have difficult battles, first against Turkey. And if we win, I think it will be against Italy. We will see. In March we will be prepared, it will be a battle, it will be great for football fans.”
Portugal host Turkey on March 24 while Italy entertain North Macedonia, with the final five days later.
At least one of the last two European champions will not make it to the World Cup in Qatar from November 21 to December 18.
“That’s life, there are no perfect scenarios. We have to face things as they are,” said Ronaldo, who has experienced a mixed return to Old Trafford this season.
While his personal return of 14 goals in 21 games in all competitions is impressive, the United are struggling down in seventh place in the Premier League, although they have reached the Champions League last 16 and FA Cup fourth round.