OMG ISS Share definition Flag When somebody says something really stupid,OMG ISS is what you should reply with. It stands for OH MY GOD. I'M SO SURE! Drunk guy at the bar "Will you pleeaaasse take me home with you?" Michelle "OMG ISS!" OMG ISS by Sosure March 24, 2010 0 0 Get merch Get the OMG ISS mug. Buy Now — $32.95 See more merch