Bruno Lage's side will be looking to bounce back at Estadio Municipal de La Linea de la Concepcion after their defeat to League One outfit Crewe Alexandra at the weekend.
Having replaced Nuno Espirito Santo as head coach, Lage is under pressure to make an instant impact at Molineux during a summer of transition.
The Portuguese opted to use a 4-4-2 formation in his opening fixture against Crewe, a change of system which did not have its desired effect as Wolves succumbed by a 1-0 scoreline.
Nevertheless, the result and performance should be put into context as Raul Jimenez made his long-awaited return from a fractured skull and the majority of the squad being made up of prospects and fringe members.
As Wolves step up the level of opposition, Lage will expect the same from his players, stressing that there are places in his squad up for grabs at a time when the club will be planning new signings.
From Betis' perspective, this is the first of three games against English teams as they prepare for a season which will also include participation in the Europa League.
Manuel Pellegrini guided his team to sixth spot in La Liga last season, and the next target will be trying to make an unlikely bid for the top four.
Before the triple-header with Wolves, Derby County and Leeds United, Los Verdiblancos were able to get their pre-season underway with a 4-0 triumph over Swiss side Winterthur.
Pellegrini used different lineups for the first and second halves against Winterthur with the stronger side appearing during the opening 45 minutes.
Like Wolves, Betis are likely to extend some of their players to at least 60 minutes in this game.
Head To Head
While Wolves have never squared off against Betis in a competitive match, they are no strangers to facing Spanish opposition.
Two of Wolves' fixtures in the 2019-20 Europa League knockout stages came against teams from La Liga.
Despite cruising through a last-32 tie with Espanyol, a tired-looking side succumbed to a late Sevilla goal at the quarter-final stage.
We say: Real Betis 2-1 Wolverhampton Wanderers
While Wolves can only benefit from their workout last weekend, facing Betis in Spain is a big step up in class. Taking everything into consideration, it would come as little surprise if the English side lost out by a narrow scoreline.