- Ability over Appearance: Asterix and Obelix are famous for being a thin short guy/tall fat guy duo, yet Guillaume Canet and Gilles Lellouche have similar height (in fact, Lellouche is a tiny bit shorter than Canet despite playing Obelix), and Lellouche is definitively not overweight (it's obvious on-screen he's an average built man wearing a costume with belly padding).
- All-Star Cast: Not only nearly all main characters are played by famous actors, but an athlete (Zlatan Ibrahimovic as Antivirus) and quite a few influencers and youtubers were cast in minor roles.
- Ascended Fanon "The magic potion is an addictive drug" is a common element in darker Asterix parodies. Here, it's actually used as a plot point (Asterix feels he's worthless without it).
- Fake Nationality:
- Linh-Dan Pham (who played the Empress) is of Vietnamese descent, not Chinese.
- Zlatan Ibrahimovic is not Italian, being Swedish, but played Roman soldier Antivirus.
- The Other Darrin: For the first time in the film series, not a single actor from the previous film returned for his/her role.
- Édouard Baer is replaced by Guillaume Canet as Asterix.
- Obelix is the very last character from the first film way back in 1999 to be recast, with Gérard Depardieu being replaced by Gilles Lellouche.
- Fabrice Luchini is replaced by Vincent Cassel as Julius Caesar.
- For Vitalstatistix, the late Michel Duchaussoy was replaced by Jérôme Commandeur.
- Getafix was played by the late Jean-Pierre Cassel in Asterix at the Olympic Games and Pierre Richard here.
- Marion Cotillard replaces Monica Bellucci as Cleopatra VII from Asterix & Obelix: Mission Cleopatra (which released 21 years earlier).
- Belgian singer Angèle replaces Laetitia Casta as Panacea from Asterix & Obelix Take on Caesar (which released 24 years earlier).
- Cacofonix was played by Franck Dubosc in Asterix at the Olympic Games and Philippe Katerine here.
- In the Latin American Spanish dub, Mario Castañeda replace the late Luis Alfonso Mendoza as Asterix.
- Reality Subtext: Getafix using a tree branch as a walking stick isn't just an artistic choice. Pierre Richard suffered from a severe osteoarthritis attack at the time of the shooting, the tree branch prop he uses as a cane replaces the real crutches he came to the film set with.
- Real-Life Relative: Guillaume Canet (the director and the actor who played Asterix) and Marion Cotillard (the actress playing Cleopatra) are in a relationship since 2007.
- Sequel Gap: Came out 11 years after the previous one, Asterix & Obelix: God Save Britannia.
- What Could Have Been: Guillaume Canet first considered to play the part of Caesar as Cleopatra is his concubine Marion Cotillard, before he ended up as Asterix.
- You Look Familiar:
- José Garcia as the Gaul Biopix. He played the Roman Couverdepus in Asterix at the Olympic Games.
- Gérard Darmon is the narrator. He played Criminalis/Artifis way back in Asterix & Obelix: Mission Cleopatra.
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