The clash is the first of several matches in the International Champions Cup, which will also see them take on Roma and Manchester United while in America.
With the players returning to pre-season training at different times, due to the disruption of a summer World Cup in Brazil, it is difficult to predict what sort of side Carlo Ancelotti will field.
However, one thing is sure: The Italian will use the match against Inter to utilise all the players, at one point, who have made the journey across the Atlantic with Madrid.
And that could mean there could be several academy players involved, with eight travelling with the squad and one, according to Madrid-based newspaper Marca, particularly impressing Ancelotti.
That one is a tall midfielder named Marcos Llorente, whose father, Paco, previously played for Los Blancos.
Marca say Ancelotti is "bowled over" by the youngster, and they suggest he could be set for big things if he continues in a similar manner: "Ancelotti is as taken aback as he was last year with Jese. If the boy from the Canary Islands was the big sensation and the youth team darling last summer, it will be of surprise to very few if he gives Marcos the same treatment."
Some things are certain, though: Madrid will be without several of their big stars, including Cristiano Ronaldo and new signings James Rodriguez and Toni Kroos.
None of the three have joined up with the squad in the States yet.
Marcelo, Raphael Varane, Angel Di Maria and Karim Benzema will also not be at Ancelotti's disposal for the Inter game.
Four goalkeepers are currently with the first team squad, though—Diego Lopez, Jesus Fernandez, Pacheco and Iker Casillas—with it most likely that Lopez, who wasn't involved at the World Cup, will be used from the off.
Across the back four, it is likely Ancelotti will play a mix of experience and youth, with eight defenders currently in training.
Here are two possible combinations he could try in each half:
Carvalho, Pepe, Derik, Nacho
Arbeloa, Ramos, D. Llorente, Coentrao
Further forward there are fewer options, and the Madrid boss may opt to choose a midfield trio using three players who have had more time off than most this summer.
Therefore, Asier Illarramendi, Marcos Llorente and Omar Mascarell may start the match, before giving way to the likes of Xabi Alonso and Luka Modric.
Devoid of their big stars, Gareth Bale can then take centre stage across the forward line.
The Welshman may well be joined by Isco, who is also fresh from a summer off, while one of Raul de Tomas or Sobrino may be given a starting berth in the No. 9. role.
Madrid squad in America:
Goalkeepers: Diego Lopez, Jesus Fernandez, Pacheco, Iker Casillas*
Defenders: Pepe, Dani Carvajal, Fabio Coentrao, Alvaro Arbeloa, Nacho Fernandez, Diego Llorente, Derik Osede, Sergio Ramos*
Midfielders: Gareth Bale, Xabi Alonso, Isco, Asier Illarramendi, Marcos Llorente, Alvaro Medran, Lucas Vazquez, Omar Mascarell, Luka Modric*
Forwards: Sobrino and Raul de Tomas.
Absent: Marcelo, Raphael Varane, Toni Kroos, Angel Di Maria, Cristiano Ronaldo, James Rodriguez, Karim Benzema
*only just joined up with the squad in the USA
Like the new article format? Send us feedback!