The Croatian side have the upper hand after they claimed a narrow 1-0 win at the Estadio Benito Villamarin last week.
Match preview
Dinamo Zagreb created a little piece of history in the first leg, as they edged out Betis to record their first-ever away win against Spanish opposition in UEFA competitions.
The Croatian champions have lost on all of their previous seven trips to Spain, but that changed when Bruno Petkovic netted a 75th-minute penalty to secure a precious victory in Andalusia.
Petkovic repeated the feat in Saturday's home league meeting with Varazdin, scoring a first-half spot-kick to guide his team to another 1-0 win.
Dinamo Zagreb have won four of their last five competitive matches (D1), and Sergej Jakirovic will certainly be pleased with the fact his team have kept clean sheets in each of those four victories.
With Dinamo Zagreb looking to protect their first-leg advantage, they will be encouraged by the fact they have lost just one of their previous eight competitive home matches (W6, D1).
After dropping down from the Europa League, Betis will have to overturn a deficit if they want to extend their first experience of the Europa Conference League beyond the knockout round playoffs.
Los Verdiblancos followed the first-leg defeat with an underwhelming goalless draw in Saturday's league meeting with Alaves - a result that extended their winless home run to four matches.
Although their recent home form will be a cause for concern, Betis have at least managed to win their last two away games against Mallorca and Cadiz.
However, they experienced mixed fortunes on their travels in the Europa League group stage, losing to Rangers and Sparta Prague while claiming a narrow victory over Aris Limassol.
Betis will hope they can produce a strong away performance in Croatia, as they bid to reach the last 16 of a UEFA Competiton for a third consecutive season.
Dinamo Zagreb Europa Conference League form:
L
L
L
W
W
W
Dinamo Zagreb form (all competitions):
L
W
W
D
W
W
Real Betis Europa Conference League form:
L
Real Betis form (all competitions):
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W
D
W
L
D
Team News
The hosts are expected to be without Bosko Sutalo, Marko Rog, Luka Stojkovic, Josip Drmic and Sadegh Moharrami due to injury.
After making a number of changes at the weekend, Jakirovic could be tempted to revert back to the side that started the first leg.
Petkovic will continue to lead the line for the hosts, with the 29-year-old looking to continue his fine spell of form after scoring four goals across the last three matches.
As for the visitors, their injury list features Abner, Marc Batra, Isco, Guido Rodriguez and Ayoze Perez, while winter additions Pablo Fornals and Chimy Avila have not been registered for the Europa Conference League.
The Spanish side are also unable to call upon German Pezzella, who will serve a one-match suspension due to an accumulation of yellow cards.
Cedric Bakambu is set to provide Manuel Pellegrini with a useful option off the bench after making his debut as a substitute in the goalless draw with Alaves.
Dinamo Zagreb possible starting lineup:
Nevistic; Ristovski, Theophile-Catherine, Bernauer, Perkovic; Bulat, Misic; Kaneko, Baturina, Hoxha; Petkovic
Real Betis possible starting lineup:
Silva; Ruibal, Riad, Sokratis, Miranda; Johnny, Roca; Rodri, Fekir, Ezzalzouli; Willian Jose