Substrate is the word used to describe a surface or material in which organisms, such as fungi, can grow and live.
In The Last of Us, it is mentioned in connection to a flour and grain factory. This is where the Cordyceps virus that is infecting people is believed to have originated.
To better understand how this all connects with the Cordyceps virus, you’ll also need to understand Mycology and its place in The Last of Us TV show.

Essentially, when Ibu Ratna, the Mycologist played by Christine Hakim, calls the flour and grain factory the “perfect substrate,” she is saying that it is a great breeding ground for the Cordyceps virus to spread.
This helps us understand exactly how the Cordyceps virus began to spread in the first place. Wheat, which will be used in the factory to make flour, is often infected by fungus.
In fact, fungal infections are a large reason why so many wheat crops die. So, it’s understandable why the Cordyceps virus, which is fungal in nature, managed to infect the wheat at the factory.

The use of the word substrate in The Last of Us may have felt like it was there to confuse you. However, it’s actually in an attempt to make the virus feel more authentic.
When talking about why they changed the origin of the infection from spores to tendrils, showrunners Craig Mazin and Neil Druckmann said it was to make it feel more believable in today’s society.
The terminology used by the Mycologist in The Last of Us TV show certainly helps to ground it, especially for any fungi experts out there.