Having lost each of their four matches so far, the home side will be playing just for pride, while the visitors could move into first place with all three points.
Match preview
Having featured in the 2020 and 2021 Copa Sudamericana, Metropolitanos clinched their first-ever Primera Division title last year to book their spot in the 2023 Copa Libertadores.
Drawn in Group B, the Venezuelan champion have received a baptism of fire in the continental showpiece, losing each of their opening four games and suffering an early exit.
Breaching opposing defences has not been the root of Metropolitanos' problems as they have made the net ripple in three of their four matches, but they have conceded nine goals so far.
Jose Maria Morr's men, who are currently rooted to the bottom of Group B, were last in action on May 26, when they suffered a 2-1 defeat at the hands of group leaders Internacional.
However, Metropolitanos are in contrasting form in the Venezuelan Primera Division, where they won three of their last four matches and sit fifth in the table with 22 points from 14 matches.
After stumbling into the campaign, a run of two wins in their last two matches has put Independiente Medellin back in contention for a place in the knockout stages.
Sebastian Botero's men picked up one point from their opening two matches before claiming a resounding 4-2 victory over Metropolitanos at the Estadio Atanasio Girardot on May 4.
This was followed by a 2-1 comeback win over Nacional three weeks later, when Andres Ibarguen and Deinner Quinones scored to cancel out Diego Rodriguez's 12th-minute opener to see off the Uruguayan side.
With just two games left to play, Independiente Medellin are currently level on seven points with third-placed Nacional and two points behind group leaders Internacional.
The Colombian side must avoid any slip-up as they look to make a first knockout-stage appearance since 2005, when they reached the round of 16 before suffering a 5-0 thrashing at the hands of Banfield.
However, Medellin have failed to win any of their last three matches, losing twice and claiming one draw — all in the Primera A, where they are currently seventh in the table with 29 points from 20 matches.
Metropolitanos Copa Libertadores form:
L
L
L
L
Metropolitanos form (all competitions):
D
L
L
L
L
L
Independiente Medellin Copa Libertadores form:
D
W
D
L
W
W
Team News
Giovanny Sequera picked up a straight red in the game against Internacional on May 26 and the 17-year-old midfielder will sit out Thursday's game through suspension.
On the injury front, Carlos Cermeno is a major doubt for Metropolitanos after the Venezuelan international was forced off injured in the aforementioned game.
Should he fail to shake off the injury, 23-year-old Francisco Bareiro could be handed his first start in the competition, teaming up with Edwin Laszo and Christian Larotonda in midfield.
Botero could name a similar side that beat Nacional in their last group outings, meaning we could see a Medellin back four of Jonathan Marulanda, Victor Moreno, Andres Cadavid and Daniel Londono for the third straight group game.
Luciano Pons is the visitors' top scorer in the group stages and the 33-year-old striker should lead the attack once again, alongside Edwuin Cetre and former Santos Laguna man Ibarguen.
Metropolitanos possible starting lineup:
Schiavone; J Vargas, Ferro, Moreno, Cova; Bareiro, Laszo, Larotonda; Gomez, F Vargas, Ortiz
Independiente Medellin possible starting lineup:
Vasquez; Marulanda, Moreno, Cadavid, Londono; Cambindo, Torres, Alvarado; Cetre, Ibarguen, Pons
We say: Metropolitanos 0-2 Independiente Medellin
While Independiente Medellin have struggled for results in recent weeks, they will be backing themselves to see off an inexperienced Metropolitanos side who have lost all four games so far. We predict the visitors will pick up a third consecutive group win and edge closer to the knockout stages.