The closest thing I can compare it to is Ulysses, by James Joyce.
I'm aware this is a melodramatic claim, but I mean it in a sense that they're both wonderfully well-written and more concerned about breaking self-limiting perceptions about art and other things than it is about telling a straightforward story. I mean, it's cool. You need a novel like that every 50 years or so and Jerusalem is that for our time. So what it is about? Well, it's difficult to say. I would say it's about how immaterial reality affects material reality and how these two planes are just as real. It's told (mostly) as the history of Moore's hometown of Northampton and through two characters who are brother and sister: Mick and Alma Warren. You don't follow them for a lot of the novel, but you kind of have to read it to understand.
Jerusalem is also really three novels: The Boroughs (the history of the place or genetic mythology as Moore puts it), Mansoul (kind of like Peter Pan on LSD) and Vernall's Inquest (where Moore makes his more cerebral points about language and reality). I know it's one novel and those fold intricately into one another, but it's also three novels if you want it to be. Solve et Coagula. If you know, you know. Is it a mandatory read? Absolutely not, even if you're an Alan Moore completist. We're not in Infinite Jest territory here. Am I happy that I read it? Yes. Even thought it seems to have sold well, I doubt even half of the people who bought the book have actually read it. It's that demanding.
Also, I would highly suggest watching Wisecrack's YouTube video called "The Philosophy of Alan Moore" before reading Jerusalem. It gives you a proper canvas to understand what the hell is going on.