La Albiceleste have suffered heartbreak in the latter stages of major competitions in recent years, but they head into this summer's tournament in Brazil as second-favourites behind only the host nation.
It is now 26 years since Argentina last won a major trophy of any description, with the 1993 Copa America their last piece of notable silverware.
It is in the past 15 years that the real international heartbreak has come, though, and even at the start of this campaign there will be a sense of foreboding about what might be in store; Argentina fans and players simply may not be able to cope with another near-miss.
Lionel Messi has twice now considered walking away from international duty altogether as a result of recent events at major tournaments, having lost the finals of the 2014 World Cup and then the 2015 and 2016 Copa America editions.
On both occasions the Barcelona icon has returned to the fold, and the hope is that this will not be the last we see of him on the world stage given that Argentina are co-hosting another edition of the Copa America next year.
Messi's own personal disappointments are only a fraction of the hurt suffered by Argentina recently, with the two-time world champions having remarkably finished as runners-up in four of the last five Copa America tournaments.
The ongoing drought has allowed Uruguay to leapfrog Argentina as the most successful Copa America nation, but a squad containing the likes of Messi, Sergio Aguero, Paulo Dybala and Angel di Maria can never be ruled out and that attacking prowess is reflected in their ranking as second-favourites.
The main question, as usual, is whether Argentina have enough talent around that frontline to challenge for honours again, and it will not be lost on manager Lionel Scaloni that their last two matches against fellow Copa America nations have ended in defeat - to Venezuela in March and Brazil last October.
Indeed, Argentina have not beaten a fellow South American team since their dramatic Messi-inspired 3-1 triumph over Ecuador in October 2017 - a result which sealed their place at the 2018 World Cup.
There have been positives since crashing out at the last-16 stage in Russia, though, with six wins, six clean sheets and only two defeats in their nine outings over the past year.
Scaloni's side only had one warm-up match for this tournament, with Messi scoring twice as they cruised to a 5-1 win over Nicaragua, and the FIFA rankings suggest that they should be favourites to qualify as winners of their group too.
La Albiceleste have been drawn alongside Paraguay and guest nation Qatar in addition to Saturday's match against Colombia, which on paper is their toughest contest of the lot - and indeed their toughest match since the World Cup.
Victory should put Argentina firmly on course to win the group, but defeat could leave them fearing another disappointing showing on the international stage.
Recent form: LWWLWW
There is a certain degree of intrigue as to how Colombia will fare at this summer's tournament, with the team still getting to grips with new boss Carlos Queiroz.
The former Real Madrid coach and Manchester United assistant only took over in February, since when he has overseen three wins from four friendlies, with each victory being accompanied by a clean sheet.
South Korea are the only team to have beaten Colombia under Queiroz so far, but they returned to form during their warm-up matches with back-to-back 3-0 victories over Panama and Peru.
Plenty of parallels can be drawn between Colombia and Argentina, both of whom rely mainly on outstanding individual attacking talent - Colombia being able to call upon Radamel Falcao, James Rodriguez and Juan Cuadrado.
Both Falcao and Cuadrado are now the wrong side of 30, though, and this could be one of their final chances at international glory - although they are also co-hosting next year's tournament alongside Argentina.
Even Los Cafeteros have won silverware more recently than Saturday's opponents, though, picking up their one and only Copa America success in 2001.
Colombia finished third at the most recent edition of the tournament and also made it to the knockout stages of last summer's World Cup before their run was ended on penalties by England in the round-of-16.
Since then they have lost just once in eight matches - winning six - and notably the majority of those games have come against higher-calibre opposition to those faced by Argentina over the past 12 months.
Whether that stands them in better stead for Saturday's opener remains to be seen but, considering the job Queiroz did while in charge of Iran, Colombia may be backed as dark horses for the tournament by many.
The first hurdle is, of course, to progress from their pool, but victory against Argentina would set them up well for the rest of the tournament and put them in pole position to qualify as group winners.
Recent form: WWWLWW
The main question for Scaloni to answer heading into this match is who to start in the attacking positions, with a wealth of talent to choose from.
Messi is perhaps the only attacker to be guaranteed a starting role, with Lautaro Martinez having staked his claim for a place ahead of Aguero by coming off the bench to score twice against Nicaragua.
Dybala is in the unfortunate position of having to directly compete with Messi for a spot and so may be forced to settle for place on the bench, while Watford's Roberto Pereyra could be preferred to the vastly experienced Di Maria.
In-demand Giovani Lo Celso will be hopeful of grabbing any chance he gets to advance his burgeoning reputation following a fine campaign for Real Betis.
As for Colombia, Queiroz must decide whether to start with captain and talisman Falcao or the in-form Duvan Zapata, who scored 23 Serie A goals in 2018-19.
Rodriguez and Cuadrado are also expected to start, while Mateus Uribe's brace against Peru in the final warm-up game may be enough to earn him a place.
Argentina possible starting lineup:
Armani; Saravia, Otamendi, Pezzella, Acuna; Rodriguez, Paredes; Lo Celso, Messi, Pereyra; Aguero
Colombia possible starting lineup:
Ospina; Arias, Sanchez, Mina, Tesillo; Cuadrado, Barrios, Uribe; Rodriguez, Falcao, Muriel
Head To Head
Argentina are unbeaten in their last eight meetings with Colombia across all competitions, winning five of those in a run which stretches back to November 2007.
Indeed, Colombia have only scored once across those eight games, failing to find the back of the net in their last five editions of this fixture since 2011.
The last two Copa America meetings between the two sides have ended goalless, and Colombia are winless against Argentina in this competition since 1999.
We say: Argentina 2-1 Colombia
This is arguably the marquee tie of the entire Copa America group stage, but it is likely to be a tight affair. Both sides have plenty of attacking firepower but questions elsewhere, and it is one which could easily go either way. We are just giving the edge to Argentina because of the Messi factor.
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