Wow... So this book is chocked full of more ideas and terminology and description and nuance than you can possibly expect before opening it up. My advice: take your time with it. This isn't an "easy" book to read. And don't expect to read a story that you can then relate to other people. In a way, you shouldn't expect a plot, as such.
As others have said, knowing some basic philosophy (Greek and Buddhist) definitely helps. Go read up on any characters you encounter that you don't know. Also, don't expect this story to actually line up with history. Despite its historical characters, it's still a NOVEL, so suspend your disbelief! It's worth it~
The journey is what it's all about in 10 Billion Days & 100 Billion Nights. Don't be afraid to read and reread and rereread passages. There are a lot of lights, and a lot of colors, and a lot of gadgets, but once you arrive at the destination (which, by the way, is not until the very very end), you will find it to be an inherently intimate and important story. It gets you way down deep in your core (also the commentary at the end by Mamoru Oshii is worth reading, it really makes the crux of the book hit ya hard)
So open it up, hold on, and prepare to sit and think for a long time once you're done!