Gustavo Santaolalla, the music composer for video games The Last of Us (2013) and The Last of Us: Part II (2020), was brought on to compose the series soundtrack.
In the games, the fungus is spreading through spores in the air. For the show, they were replaced with tendrils. Neil Druckmann explained that this was a deliberate decision he made early on during the show's development, as he wanted to make the world more believable and the fungus more frightening.
The Mandalorian (2019) producers gave Pedro Pascal permission to work on the series. He is reportedly earning $600,000 per episode, making him one of the highest-paid American television stars.
A non-gamer, Pedro Pascal watched his nephew play the beginning of the first game because he lacked the skill to play it himself; he found Joel to be "so impressive" but was concerned about imitating the games too closely, instead choosing to "create a healthy distance" and allow the showrunners to decide the characterization.
In the first season, Merle Dandridge and Laura Bailey reprised their roles as Marlene and Firefly nurse respectively.