The two sides drew 0-0 in Peru last week, making the Brazilians favourites to progress on home soil on Thursday.
Match preview
Indeed, given that their striker Alexandre Zurawski was sent-off in the 64th minute, Internacional would have been pleased to escape Peru with a draw.
The hosts had 20 shots - nine of which were on target - and 63% possession across the 90 minutes, with goalkeeper Daniel undoubtedly man of the match having kept a clean sheet despite being bombarded.
Mano Menezes, who has been head coach of Internacional since April, will be hoping for more offensively from his side on Thursday, which should be a given in front of a raucous Estádio Beira-Rio atmosphere.
The Red are unbeaten there in five games in all competitions, so will feel confident of reaching the Copa Sudamericana semi-finals as they look to win the competition for the second time in the club's history.
Melgar, meanwhile, have already made history with this being their best ever performance in a continental competition.
Indeed, this is the first time they have ever made it to the quarter-finals of either the Copa Libertadores or Copa Sudamericana, having competed in both tournaments six times apiece in the past.
The Domino have received huge praise in their home country for their efforts, which have been built on a solid foundation of excellent recruitment and strategy behind the scenes.
Head coach Pablo Lavallen, who only joined the club earlier this year, will be calling on a big performance from his players as they travel to Porto Alegre.
Should they perform as well as they did last week despite being held to a draw, there is every chance they can pull off a major upset.
Internacional Copa Sudamericana form:
Internacional form (all competitions):
Melgar Copa Sudamericana form:
Melgar form (all competitions):
Team News
Internacional will be without Zurawski through suspension after the forward's straight red card in last week's first leg.
Menezes could look to Braian Romero to replace him in attack, but Caio Vidal and Rodrigo Moledo are unlikely to recover from injury in time to make the squad.
Melgar, meanwhile, will travel without defenders Leonel Galeano and Pedro Ibanez due to injury.
Lavallen is unlikely to make any changes from the XI which exceeded expectations on home soil last week.
Internacional possible starting lineup:
Daniel; Bustos, Vitao, Mercado, Rene; Gabriel, Maurcio, De Pena; Edenilson, Romero, Wanderson
Melgar possible starting lineup:
Caceda; Ramos, Deneumostier, Lazo, Reyna; Orzan, Arias, Guedes; Bordacahar, Cuesta, Cabrera
We say: Internacional 2-0 Melgar
Melgar have had a record-breaking run in this season's Copa Sudamericana, but we think it is likely to come to an end in Porto Alegre on Thursday.
The hosts have more individual quality and, providing they keep their cool with 11-men on the pitch, should have too much in front of their home fans.