The film was originally conceived as a reboot of the "Predator" film franchise, until Shane Black came aboard and confirmed he would be making a sequel instead, as he wanted to continue to explore the "Predator" mythology.

The film was directed and co-written by Shane Black, as a sequel to Predator (1987), Predator 2 (1990) and Predators (2010). Shane Black had played Hawkins in the original film.

After the success of Iron Man 3 (2013), Shane Black was approached by 20th Century Fox with an Iron Man 3 (2013)-sized budget to direct a new "Predator" movie, and he could not resist.

Shane Black had gone on record stating he wanted this movie to be true to the spirit of the franchise, and for it to be R-rated, saying, "It's an odd thing. Whether Deadpool (2016) helped is an open question, but I suspect it did. I made a condition of my participation with 'Predator,' that it be the same rating as the first movie, and the first movie was rated R. In other words, I don't want to cut away every time the Predator does something violent. I was watching the American version of The Grudge (2004), which was PG-13, and I remember being so frustrated by the fact that everything that was scary in the Japanese version, they had to cut away from in the PG-13 American version."

Shane Black was cast in the original film, with the intention that he would re-write the script during production. However, he chose not to do so and the script was not rewritten.

Adrien Brody expressed interest in reprising his role from Predators (2010).

Benicio Del Toro was originally supposed to star, but he was replaced by Boyd Holbrook due to scheduling conflicts.

Arnold Schwarzenegger turned down the opportunity to return as Dutch.

This film marked the sixth time the Predator appeared in a theatrical release, after Predator (1987), Predator 2 (1990), AVP: Alien vs. Predator (2004), Aliens vs. Predator: Requiem (2007) and Predators (2010).

Jake Busey plays the son of Peter Keyes, the government official from Predator 2 (1990) who died during the hunt for the Predator. Peter Keyes was played by Gary Busey, who is Jake's father in real life as well.

The slogan in the teaser poster, "You'll never see him coming," was an obvious reference to the Predator's cloak, but also a nod to Iron Man 3 (2013), which was written and directed by Shane Black, in which the character of The Mandarin notably uses the line, "You'll never see me coming..."

Sterling K. Brown, Thomas Jane, Olivia Munn and Boyd Holbrook all starred in a Marvel movie. Brown was in Black Panther (2018), Jane was in The Punisher (2004), Munn was in X-Men: Apocalypse (2016), and Holbrook was in Logan (2017).

Boyd Holbrook and Trevante Rhodes were both cut from the film Song to Song (2017).

The poster of this film had the slogan, "You'll never see him coming." This was a quote similar to one said by the character The Mandarin in Iron Man 3 (2013), "And you'll never see me coming." Both The Predator (2018) and Iron Man 3 (2013) were written and directed by Shane Black.

The Predator shown in the teaser poster is actually the Crucified Predator from Predators (2010), identifiable by the damage to its Bio-Mask.