Me and my girlfriend used Runners in the Shadows to homebrew a Warhammer 40k Necromunda game. It worked really well, I made the rules work with the setting and story we wanted to play, she was the GM and made the runs. I had prior experience with Blades so I was able to understand what the rules were doing and tweak them as required to make them fit 40k. Each runner used a custom playbook I designed for their character concept.

I really like the Blades systems in general, but you are going to run into some mechanics that don’t mesh (we had issues with defining how cyberware operated in Runners for example. We didn’t run Scum and Villainy proper as we were just kind of winging it at that point, but I feel like they do a good job of letting players come up with their own ideas if a mechanic doesn’t work for them. There are also Foundry/Forge modules for Blades and subsystems. I say go for it.