Los Cuatro Fantasticos, as fans call them, are all 26, came through Argentina’s ranks together and are hitting the peak of their careers.
Coach Alejandro Sabella is spoiled for choice as he takes his fancied team to the World Cup to take on Nigeria, Bosnia and Iran in Group F.
Barcelona’s Messi has deposed Diego Maradona as Argentina’s leading scorer — with 37 strikes in 85 appearances — and is rated as the world’s most valuable footballer.
Higuain, of Italian side Napoli, has 22 goals from 36 internationals; Aguero, who has just won the English title with Manchester City, 21 goals from 50 games and di Maria, triumphant in the Champions League with Real Madrid, 11 goals from 45 games.
Sabella could play them any way he wants and that kind of firepower has made Argentina second favourites to win the cup, behind Brazil.
The coach struggled however to get the right formation after he arrived in September 2011.
“Today the team plays with three attackers (Messi, Aguero and Higuain) of an extraordinary level, plus di Maria, who is a fourth attacker,” said Sabella.
Di Maria normally plays an offensive midfield role for Argentina.
“It is very difficult to take one out,” Sabella added. “But we are going to continue like this.”
Even if one of the fab four is injured, Sabella has plenty of support to fall back on.
Carlos Tevez could not even make the Argentine squad despite a brilliant season with Juventus. Sabella could not handle managing a squad with Messi and Tevez.
But he still has Rodrigo Palacio of Inter Milan and Ezequiel Lavezzi of Paris St Germain, who both got games in the 3-0 friendly win over Trinidad and Tobago on Wednesday.
Aguero and Higuain were rested for that match.
Normally Sabella plays Higuain as the target man, Aguero on the left, di Maria in midfield and Messi marauding on the right.
The lineup makes Argentina a huge threat on the counter-attack.
Messi cast aside some of the weight of playing for the national team, scoring 18 goals in his last 16 games, including World Cup qualifying.
But Sabella makes frequent changes to the formation and the rest of the team poses problems for him.
Javier Mascherano will have to carry many of the defensive duties in midfield and centre back Federico Fernandez and left-back Marcos Rojo have regularly been exposed.
The team are favourites to win their group.
Argentina will face pressure as they were the winners the last time the tournament was held in South America, in Argentina in 1978. The last time they got past the quarter finals was in 1990.
Read more here Capital Sports