On “In My Blood,” Shawn Mendes takes a heavier and more mature approach production-wise, while still sticking to his acoustic roots in the verses. The day before the release he tweeted a message to his fans saying:

This song is the closest song to my heart that I’ve ever written.

In an interview with Billboard, Mendes explained that the song is about his first experience with anxiety:

The concept of this song is about how it feels [when] you’re about to give up, and then you don’t. That’s the whole payoff in the chorus section…It’s not about when it happens. It’s kind of about something that I think everybody goes through and it’s something that I think people don’t talk about often, especially in music.