This came out of Nile's frustration at how the pandemic was handled in the US. "I'm not a big finger-pointer, but a lot of people died last year, and it didn't have to be that way," he said in a 2021 Songfacts interview
. "It could have been better. It was criminal. I just was so pissed off about it, I wrote that song one night."
He elaborated on the song meaning: "These are turbulent times. The song is about dancing with the devil, whether it's something personal between two people or politics on a world stage, if you dance with the devil, you can get blood on your hands. There's no limit to greed, selfishness and pride. They're not limited to any governments. But clearly on a larger scale, the pandemic had a devastating effect, globally on the world, as have all the wars. So that song in general has a universal theme. And to have Steve sing on 'Blood On Your Hands' meant the world to me."