The five-time Ballon d'Or winner has one of the most impressive trophy hauls in football history but there is a glaring void when it comes to national team accolades.
Four Champions League crowns and 10 La Liga titles with Barcelona are not matched by Argentina success.
And the 31-year-old knows he's running out of time to rectify that anomaly.
"I want to end my career having won something with the national team, or at least try to do so as many times as possible," he told Fox Sports last week.
Four finals played with Argentina, four defeats, including the last two Copa finals on penalties against Chile.
But the most painful was the 2014 World Cup final to Germany at the iconic Maracana, where Messi will hope to return on July 7 for the Copa title decider.
That Germany defeat began a run of losing finals in three successive years and after the last of those, a bitterly disappointed Messi announced his international retirement.
He and his team-mates came in for a torrent of criticism.
"People were attacking us from every side," he said.
His retirement lasted just six weeks, though, and it was his hat-trick in Argentina's final qualifier that secured a 3-1 win in Ecuador that sent the team to the World Cup in Russia last year.
But, as so many times before, Messi was unable to recapture his Barca form while on international duty and dejection followed as the albiceleste were sent home in the second round after a 4-3 defeat to eventual winners France.
But while Messi then missed Argentina's next six matches -- all friendlies -- there was no talk of retirement this time.
His son Thiago "loves it when I play for the national team," Messi told Fox.
But the disappointments have kept piling up despite a 10th La Liga crown secured in May.