It works equally as well with people you've known for a long time, like, say, your family. This game was brought along on my family's annual beach trip this year, and I was initially nervous, but we had a blast. There are still some things I wish I didn't know my grandma knew, and there were a few cards that were hard to read in front of my mom, but the mutual embarrassment is kind of part of the fun, honestly. If your family is all adults, or if there are kids that go to sleep early, this is for you — it's probably not a great choice to play with younger teens, though. This game is solidly 17+.
You probably noticed that the gameplay is a lot like both Apples to Apples and Cards Against Humanity, so I'll use those two as points of comparison. On an imaginary Offensiveness Scale, where Apples to Apples is a 1 and Cards Against Humanity is a 10, I'd put What Do You Meme? somewhere around an 8. It's maybe a little heavier on the sex-based jokes, but definitely has less of the ~anti-PC edgy comedy~ stuff that I find a little tiring about CAH — to put it bluntly, you might see more jokes about cum, but you aren't gonna get any about 9/11 or the Holocaust. Personally, I think this makes for a better party game, but YMMV here.