The visitors will look to extend their three-game winning run in all competitions, while the Argentinian outfit have drawn their last three matches domestically.
Argentinos Juniors qualified for this year's Copa Libertadores with a fifth-placed finish in the Argentine Primera Division last season.
While that extended their run without a domestic title, with their last trophy coming in 2010, the three-time Argentinian champions will be more than happy with continental qualification.
El Bicho have had a mixed start on the domestic front this season though, currently sitting in ninth place with twelve points from their first 10 league matches.
They salvaged a 1-1 draw against San Lorenzo last time out, as Gabriel Hauche netted an equaliser in the 72nd minute to take home a point.
The appointment of former Argentina centre-back Gabriel Milito as manager in January has failed to trigger a major upturn for Argentinos Juniors, with only three wins coming from those 10 league games in Milito's first season at the helm.
However, the Copa Libertadores gives El Bicho a chance to prove themselves against strong opposition, and Milito will be desperate for his side to make a winning start against the Uruguayan champions on Tuesday.
The visitors will look to stretch their winning run to four games with what would be an important victory to kickstart their Copa Libertadores campaign.
Nacional come into this game on the back of a 4-0 aggregate victory over Rentistas in the Uruguayan Primera Division final.
The Uruguayan giants have lifted the Copa Libertadores three times in the club's history, although their last title came in 1988.
Alejandro Cappuccio's side will have their sights set on a victory to kick off their campaign on Tuesday, as they look to qualify and boost their bid for a first title in over 30 years.
Gabriel Hauche will be pushing for a return to the Argentinos Juniors starting side on Tuesday, after he netted the equaliser off the bench last time out.
He will have to compete for a starting spot with Gabriel Avalos, who has been preferred in attack in recent weeks.
Nacional's line will be led by Gonzalo Bergessio, who netted three goals in the 4-0 aggregate victory over Rentistas.
He will be supported by the attacking threat of midfielder Felipe Carballo, who has been a key man since his January move from Spanish side Sevilla.
Argentinos Juniors possible starting lineup:
Chavez; Mac Allister, Torren, Quintana; Romero, Moyano, Vera, Gomez; Cabrera, Hauche, Carabajal
Nacional possible starting lineup:
Rochet; Mendez, Corujo, Marichal, Velazquez; Ocampo, Carballo, Martinez, Garcia; Bergessio, Vecino
We say: Argentinos Juniors 1-2 Nacional
The visitors come into this game in a strong run of form, and we see their momentum carrying them to another important victory on Tuesday.
Nacional have plenty of experience on the continental stage, and we would expect that to see them over the line in Buenos Aires.