The hosts have dropped down from the Europa League, while the Croatian side secured second spot in Group C of the Europa Conference League.
Match preview
Betis have had to settle for a place in the Europa Conference League knockout rounds after they lost their final two matches of the Europa League group stage to finish behind Rangers and Sparta Prague.
While they would have been disappointed to drop down from the Europa League, Betis may view this as a golden opportunity to win the first-ever European trophy.
Los Verdiblancos will enter the first leg off the back of a victory after goals from Willian Jose and Pablo Fornals guided them to a 2-0 win over Cadiz on Friday, moving them up to sixth place in the Spanish top flight.
Although they are now unbeaten in three matches, Manuel Pellegrini's side have struggled on home turf in recent times, having won just one of their last six competitive home games (D3, L2).
The hosts will also be concerned by the fact they have failed to win any of their last seven home matches in the knockout rounds of a UEFA competition (D2, L50.
Dinamo Zagreb are participating in the playoff round after winning three of their six group games (L3) to finish five points better off than Astana and Ballkani.
The reigning Croatian champions travel to Andalusia following a 2-2 away draw against Lokomotiva Zagreb, where they came from behind on two occasions thanks to a Bruno Petkovic brace.
However, Sergej Jakirovic may have been disappointed with the point, with his side currently sitting in third place and six points adrift of leaders Rijeka, who have played a game more.
While they have their work cut out to win a seventh consecutive league title, Dinamo Zagreb will have to put domestic matters on hold, as they turn their attention to their first meeting with Betis.
The Croatian side will be hoping to win in Spain for the first time in UEFA competition, having lost on all of their previous seven visits.
Real Betis form (all competitions):
L
W
L
W
D
W
Dinamo Zagreb Europa Conference League form:
W
L
L
L
W
W
Dinamo Zagreb form (all competitions):
W
D
L
W
W
D
Team News
Betis are unable to call upon the creative talents of Isco, who is set to be out for an extended period after recently sustaining a hamstring injury.
The former Real Madrid man is joined in the treatment room by Abner, Marc Bartra, Ayoze Perez and Guido Rodriguez.
January addition Cedric Bakambu will have to wait to make his Betis debut, with the DR Congo international set to return from the Africa Cup of Nations later in the week.
Fornals will have to drop out of the starting lineup after being left out of the squad for the Europa Conference League.
As for the visitors, they will be without the services of the injured trio of Josip Drmic, Marko Rog and Luka Stojkovic.
Takuya Ogiwara is expected to retain his place at left-back after starting the last two matches following his loan move from Urawa Red Diamonds.
Takuro Kaneko dropped down to the bench at the weekend, but the 26-year-old could return to the side after featuring as a half-time substitute in the 2-2 draw against Lokomotiv Zagreb.
Real Betis possible starting lineup:
Silva; Bellerin, Pezzella, Riad, Miranda; Johnny, Altimira; Diao, Fekir, Rodrii; Willian Jose
Dinamo Zagreb possible starting lineup:
Zagorac; Ristovski, Theophile-Catherine, Perkovic, Ogiwara; Sucic, Music; Kaneko, Baturina, Hoxha; Petkovic
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