Lighting up LaLiga and the Champions League for more than 15 years as well as netting 76 goals in 150 appearances for his country, the 34-year-old has tasted silverware on nearly all the stages he has featured on.
But nagging away at the back of his mind - in addition to his current free agent status as Barcelona look to renegotiate a new deal for him - is his empty trophy cabinet when it comes to major trophies won with his country's senior side.
Lionel Messi will get another crack at Copa America glory when Argentina face BrazilInsurance Loans Mortgage Attorney Credit Lawyer
They qualified for the final on Sunday after Emiliano Martinez saved three penalties in a shootout against Colombia
Argentina are aiming to end 28 years of hurt at this year's Copa America, having gone trophyless since their success in the same tournament in 1993.
Sunday's final against Brazil provides Argentina's No 10 and co another chance to put an end to that drought after their dramatic penalty shootout victory in the semi-final against Colombia.
And his fiery reaction to Yerry Mina's penalty miss in the semi-final shows just how crucial he considers this tournament to be. At his age, he is well aware of the fact that he is running out of chances to taste international glory.
That, imbued with the accumulated pain of losing three Copa America finals as well as the 2014 World Cup final against Germany, probably brought out ardent roars from the halfway line as Emiliano Martinez produced goalkeeping heroics.
Messi has endured frustration on the international stage, beginning with the 2007 Copa America final defeat by Brazil
He first felt the stinging pain of a major final defeat back in 2007, just a year after he had become a first-team regular at Barcelona, celebrating his 20th birthday just before the tournament got underway.
Despite the presence of Juan Riquelme and Messi's relative inexperience, Argentina manager Alfio Basile was not afraid to chuck the latter in at the deep end and he did not disappoint.Insurance Loans Mortgage Attorney Credit Lawyer
The prodigious youngster started the opening game against Colombia and provided an assist for Hernan Crespo's second goal against the USA, with Argentina going on to win three group games out of three.
A quarter-final victory against Peru saw Messi net his first Copa America goal, but it was overshadowed soon after by his simply sublime chip in the semi-final against Mexico to set up a final against Brazil in Venezuela.
But having taken the tournament by storm so far, it all came to a crushing and devastating end for Messi and his team-mates at the final hurdle, suffering a brutal 3-0 defeat as Julio Baptista, Roberto Ayala and Dani Alves netted for the five-time world champions.
Messi started the 2014 World Cup well but many claimed they were disappointed with his displays in the knockouts
Argentina were eventually defeated by Germany in the World Cup final at the Maracana
Messi nevertheless went on to establish himself as one of, if not the best player on the planet in the following years at Pep Guardiola's Barcelona, but that did not quite translate onto the international stage.
Argentina were knocked out at the quarter-final stage by semi-finalists Germany at the 2010 World Cup and by eventual winners Uruguay at the 2011 Copa America, going without a goal in both tournaments.
Yet hope in the national team had been restored by 2014, and Messi was at the heart of their journey to the World Cup final in Brazil.
He netted just his second World Cup goal to ensure Argentina got off to a winning start against Bosnia and Herzegovina, before yet another stunner in a major tournament.
Iran had held Argentina for more than 90 minutes but in stoppage time, Messi picked the ball up 20 yards out and curled a sumptuous effort into the far corner.
His form would continue with another two goals in their final group game, before he set up Angel Di Maria to take Argentina past Switzerland and past the last eight this time around.
He was awarded the Golden Ball in Brazil but he missed the chance to beat Manuel Neuer (left)
Gonzalo Higuain's goal was enough to see off Belgium, and Messi was one of the Argentina players to score their penalty in the shootout win against the Netherlands in the semi-final following a goalless affair in regulation and extra time.
Germany once more stood in Messi's way of international silverware, but his lack of perceived effectiveness in the knockouts had not gone unnoticed.
'I have been marginally disappointed,' former Barcelona and England striker Gary Lineker said in July 2014.
'There is something not right. He has become very static. I went to the semi-final [against Holland] in Sao Paulo and watched him closely and there is so little movement now.
'He has done magical things at this World Cup and he is largely responsible for them being in the final but he looks jaded to me.'
Yet Messi created more chances than anybody at the 2014 World Cup and only former Italy midfield maestro Andrea Pirlo played as many through-balls.
Messi's frustrations continued as Argentina were beaten on penalties by Chile in the 2015 Copa America final
Such statistics earned him the World Cup's Golden Ball as the outstanding player of the tournament, but fine margins denied him the chance at the award he really wanted and made the prize he had won seem rather bittersweet.
Having expertly collected a short pass, Messi went on one of his iconic runs down the left, before unleashing a whipped shot which beat Germany goalkeeper Manuel Neuer but also the far post. Mario Gotze would make no such mistake with his chance.