Zinedine Zidane's side have won their two away matches, at Deportivo La Coruna on the opening weekend and against Real Sociedad on Sunday, but were held at home to Valencia and Levante either side of the international break.
Los Blancos therefore have eight points from their four fixtures so far in the Primera Division and are four behind leaders Barcelona ahead of the fifth round of matches.
Here, Goal takes a look at everything you need to know ahead of Madrid's match against Betis...
REAL MADRID INJURIES
Mateo Kovacic went off with an adductor injury against APOEL last week and the Croatian midfielder is expected to be sidelined for up to two months.
Karim Benzema is also out after picking up a muscle injury in the 1-1 draw at home to Levante earlier this month, but Toni Kroos is available again after missing the trip to Anoeta on Sunday.
REAL MADRID SUSPENSIONS
Cristiano Ronaldo returns from the five-match ban he received for his red card and subsequent push on the referee in the Clasico clash at Camp Nou last month.
The Portuguese was back in action in the Champions League at home to APOEL last Tuesday, but missed the Spanish Supercopa second leg versus Barca, along with the Liga clashes against Deportivo, Valencia, Levante and Real Sociedad.
Marcelo is also available again after missing the trip to Anoeta through suspension, the Brazilian's two-match ban for his dismissal against Levante reduced to one on appeal.
REAL MADRID POTENTIAL STARTING LINE-UP
With his five-match suspension now served, Cristiano Ronaldo will return for Real Madrid in attack against Betis, with Gareth Bale set to keep his place in the team following his impressive goal at Anoeta on Sunday.
Young striker Borja Mayoral is likely to drop to the bench, with Toni Kroos back in midfield and Dani Ceballos in line for a start against his former club if coach Zinedine Zidane decides to give Luka Modric a rest.
Marcelo is back from suspension and will start at left-back.
BETIS TEAM NEWS
Betis have won two matches and lost their other two so far in the Primera Division this season and are currently 11th in the table.
The Andalusians lost their opening match 2-0 at Barcelona, before beating Celta Vigo 2-1 in their first match at home. The Seville-based side then went down 3-1 at Villarreal, but returned to winning ways with a 2-1 victory at home to Deportivo La Coruna at the weekend.
Juan Narvaez is out injured and will play no part at the Bernabeu.
BEST OPTA MATCH FACTS
Real Madrid have won 10 of their last 12 leagues games against Betis, drawing one and losing the other. Both of those matches were at the Benito Villamarin (1-1 in January 2016 and 1-0 in November 2012).
Betis have lost on their last seven visits to the Santiago Bernabeu and have not won a point away to Real Madrid since the goalless game in February 2007.
The Andalusians have not won at the Bernabeu since a 1-0 victory in October 1998.
Cristiano Ronaldo has five goals and five assists in his 10 appearances against Betis in La Liga.
Isco has scored four goals against Betis in the Primera Division, making the Andalusians his preferred rival in the competition along with Levante.
TV COVERAGE & KICK-OFF TIME
Real Madrid versus Betis kicks off at 22:00 local time at the Santiago Bernabeu on Wednesday and will be broadcast live from 20.55 UK time on Sky Sports Football.