1 (challenge, confront) meterse con (informal) if he ever messes with me again I'll kill him si vuelve a meterse conmigo lo mato (informal)
he'll have a real fight on his hands if he ever tries to mess with us again a warning to any future quarrelsome customers who attempted to mess with them do you know who you're messing with? - do you know who I am?
2 (interfere with) interferir con the system works well so don't mess with it el sistema funciona bien así que no interfieras con él
you are messing with people's religion and they don't like that
3 (get involved with) I used to mess with drugs estaba metido en drogas (informal)
I don't want to mess with ouija boards and ghosts again Clinton didn't know what he was messing with when he took on this issue