Both teams head into the game looking to steal an early march on the other ahead of the second leg which is set to take place next week.
Match preview
Nacional rounded off an underwhelming Copa Libertadores group-stage campaign with an emphatic 3-0 demolition of Brazilian outfit Bragantino on May 24.
First-half strikes from Alfonso Trezza and Camilo Candido put Pablo Repetto's men in the driving seat before a late own goal from Cleiton sealed the deal.
Since then, Bolsilludo have won four of their subsequent five league games and currently sit top of Group B in the Uruguayan Premier Division.
The Montevideo-based outfit now shift their attention to continental commitment, where they will be aiming to advance past the round of 16 stage, which spelt the end of the road for them last time out.
Having won their last four home games by an aggregate score of 11-0, Tuesday's hosts are well-placed to get the job done and secure a first-leg advantage.
Union de Santa Fe breezed past the challenge of Atletico Junior in their final Copa Sudamericana Group H fixture at the Estadio Metropolitano Roberto Melendez.
Gustavo Munua's men took the lead early on thanks to an own goal from Omar Albornoz before strikes from Jonatan Alvez, Kevin Zenon and Matias Gallegos sealed the deal.
However, El Tate have only managed to pick up seven points from the following five league games and are in 12th place in the Argentine Primera Division as things stand.
Off the back of an impressive triumph over Boca Juniors in their last away fixture, Tuesday's visitors set out to record another feather in the cap on the road.
Nacional Copa Sudamericana form:
Nacional form (all competitions):
Union Copa Sudamericana form:
Union form (all competitions):
Team News
Camilo Candido was absent from Nacional's last league outing through suspension, but the defender is eligible to participate on Tuesday.
With three continental goals to his name in six games this term, Emanuel Gigliotti will be looking to come up trumps for the home side once more.
After coming off the bench to good effect in Union's triumph over Boca Juniors on Saturday, Franco Troyansky could be handed a place in the starting XI.
Jonatan Alvez will be a huge miss for the visitors off the back of a four-game scoring streak prior to his muscle injury which he picked a week ago.
Nacional possible starting lineup:
Rochet; Lozano, Marichal, Laborda, J. Rodriguez; Castro, Y. Rodriguez, Carballo, Zabala; Gigliotti, Fagundez
Union possible starting lineup:
Moyano; Esquivel, Britez, Aguero, Gerometta; Juarez, Portillo, Nardoni, Machuca; Canete, Gallegos