The development of Alien: Romulus began during the production of Alien: Covenant, when Fede Álvarez contacted a producer at Ridley Scott's production company Scott Free and submitted the idea for the film. Ridley Scott liked the treatment, but due to his own plans for the Alien series, an earlier production was unfavorable. After Disney's acquisition of 21st Century Fox, plans for several franchise projects, including Alien, were announced. Álvarez was contacted in the spring of 2022, and in March 2022, he officially took on the directing and screenwriting duties.

In designing the film, Álvarez and his team were keen to return to the original form of the Alien films, drawing on concepts from the original artists such as Ron Cobb and HR Giger. Filming took place in Budapest in 2023.

A particular challenge was the recreation of the android Rook, who resembles the android Ash from the original film and was realized using CGI and archive data from Ian Holm. Benjamin Wallfisch composed the film music, integrating themes from Alien, Aliens and Prometheus into the soundtrack.