Director Paul W.S. Anderson stated in an interview that their original plan was to produce Retribution and a sixth installment back-to-back, but he later decided to focus on just the fifth film. In the same interview, Anderson stated that if Retribution does well financially, then a sixth film would be developed and it will be the finale of the series. Milla Jovovich revealed that she is planning to star in a sixth and final installment of the franchise which will close out the series' storyline. Her husband, Anderson, pitched her the idea while vacationing following wrapping the fifth film and that the series would most likely continue past a sixth film, just not with her as the star. A sixth film was confirmed by Sony distribution's head Rory Bruer. In an interview with Forbes, producer Samuel Hadida stated that a sixth and seventh installment are planned and a reboot of the series is possible.
By the end of 2013, Milla Jovovich had been confirmed to return as Alice, and Michelle Rodriguez was also set be making another appearance. Paul Anderson had come up with a basic plot outline during the development of the previous film according to an interview with Collider. though as of February 2014 had not written a completed script. At the time the magazine estimated a release date of somewhere in Autumn 2015. Sienna Guillory confirmed on Twitter in 2015 she had not been asked to reprise her role as Jill Valentine, who appeared as a major villain in the previous film.
Shooting of the film has been significantly delayed past its early-2014 production. This was initially due to the commitments of both Milla and Paul Anderson to other film projects, with Anderson having just completed the film Pompeii in January. As a result, pre-production of the film been halted until after their filming schedules and subsequent vacation were over, with the script not being completed by February 2014. In June of that year, Anderson confirmed he was writing the first draft of the film, which he referred to under the working title Resident Evil: The Final Chapter. On August 18, 2014 Jovovich announced on her Facebook page that she's pregnant with a second child, meaning the production on the film would be delayed further. Jovovich announced on her Facebook that filming will start in August 2015. Principal photography on the film began on September 18, 2015 in Cape Town, South Africa.
A number of YouTubers who were in Capetown, South Africa for a
convention were given a chance to appear in sequences for the film as zombies.
During filming, British stuntwoman Olivia Jackson was seriously injured when she collided with a camera arm while recording a motorcycle scene, and had to have an arm amputated.