Messi stepped away from the national team following last summer's competition, but the Barcelona forward is now back in the fold and will be looking to help Argentina record their third straight win.
Argentina have played six times since last summer's World Cup, overcoming Guatemala, Iraq and Mexico (twice), in addition to drawing with Colombia and losing to Brazil; they will play twice more before this summer's Copa America - at home to Venezuela on Friday and away to Morocco on Tuesday.
There is no getting away from the fact that it was a disappointing 2018 World Cup for Argentina as they exited in the round of 16. That said, the South American country did lose to the eventual winners - suffering a 4-3 defeat to France, who went on to overcome Croatia in the final.
Argentina are two-time winners of the World Cup but have only been past the quarter-final stage on one occasion since 1994. What's more, they have not won the Copa America since 1993, but they have finished as the runners-up in four of the last five competitions, which is a record they will want to alter this summer.
Messi's return is obviously the main talking point and the 31-year-old has been in stunning form for Barcelona this season, scoring 39 times in 37 appearances in all competitions. There is still a feeling that the attacker does not really produce on the international stage, though, and that will probably not go away unless he can lead his country to success at a major competition before retirement.
Argentina's squad is once again packed full of midfield and forward talent, but their issues in defence remain. Lisandro Martinez and Gonzalo Montiel are two new faces who could earn some minutes at the back, while Domingo Blanco, Ivan Marcone, Federico Zaracho and Matias Suarez are the other uncapped players in the squad.
As mentioned, Argentina have beaten Mexico 2-0 in each of their last two friendlies, which came after the 1-0 loss to Brazil in October. Lionel Scaloni's side will open their Copa America against Colombia on June 15 and will have the next couple of matches to iron out a few details ahead of the tournament opener.
The South American nation, who will also take on Paraguay and Qatar in the group stages of the tournament, have seriously underachieved in recent years considering their talent, but Messi's return has given everyone a huge boost.
Recent form: WDWLWW
Like Argentina, Venezuela are also preparing for the 2019 Copa America; they will enter this game off the back of back-to-back draws with Japan and Iran, and La Vinotinto will follow up this game with fixtures against Catalonia and Mexico ahead of their tournament opener against Peru on June 15.
Venezuela will also take on Brazil and Bolivia in the group stages of the Copa America; they reached the quarter-finals of the competition in 2016, while they ended the 2011 tournament in fourth position.
Venezuela have never qualified for the finals of a World Cup, though, and will be the huge underdogs when it comes to Friday's game against an Argentina team who have Messi back in the fold.
Rafael Dudamel's team do have a lot of talented footballers, however, with Salomon Rondon currently enjoying a fine season with Newcastle United in the Premier League. Atlanta United's Josef Martinez is also a big talent, while Roberto Rosales of Espanyol and Tomas Rincon of Torino bring a lot of experience.
Venezuela have lost 21 of their previous 24 international games with Argentina, recording just one win. The last two meetings between the two teams have finished level, however, and La Vinotinto's sole victory came as recent as 2011.
Dudamel's side finished bottom of the South American 2018 World Cup qualification section, though, losing 10 of their 18 matches and collecting just 12 points. They did overcome Paraguay in their last competitive fixture, but it was a very disappointing qualification campaign.
It promises to be a tough encounter for Venezuela on Friday, but this is the exactly the type of fixture that they need ahead of the Copa America, which kicks off in June.
Recent form: LWLWDD
Argentina will be without the services of Angel di Maria, who has been forced to pull out of the squad due to a muscular problem.
Giovani Lo Celso and Leandro Paredes will also start, while Messi could be joined in the final third by Pity Martinez and Lautaro Martinez, leaving the likes of Paulo Dybala, Angel Correa and Manuel Lanzini on the bench.
Messi is the leading scorer in the squad with 65 goals, but the other six forwards only have four between them, which shows the huge pressure that is still on the Barcelona forward at international level.
As for Venezuela, Rondon and Martinez are both expected to start in the final third of the field, with Rincon and Rosales also earning spots in the XI further back.
Dudamel is likely to mirror Argentina's 4-3-3 formation on the night, with DC United's Junior Moreno starting at the base of the midfield.
Argentina possible starting lineup:
Armani; Montiel, Mercado, Foyth, Tagliafico; Paredes, Pereyra, Lo Celso; Messi, Lautaro Martinez, Pity Martinez
Venezuela possible starting lineup:
Farinez; Rosales, Osorio, Chancellor, Mago; Moreno, Herrera, Rincon; Murillo, Rondon, Martinez
Head To Head
As mentioned, these two nations have locked horns on 24 previous occasions, with Argentina recording 21 wins and suffering just one defeat.
The last two meetings between the two teams have finished level, however, and La Vinotinto's sole victory came as recent as 2011.
We say: Argentina 2-0 Venezuela
Argentina should have more than enough to record their third straight win, but Venezuela are not to be underestimated and it could be a tough game for the home side.