I have Fallout 4 and bought the retail disk from Best Buy. The game is something like 30GB in size... a DVD holds just over 4GB, or 9+GB if it's double layer. Plus you have mandatory updates that have to be downloaded and installed before you can begin playing. You need, at least, an internet connect for the initial install, updating, and activation. Once you do that, I think you should be able to play.
Here is a Quote to confirm what I just said:
"... Pete Hines, Bethesda's marketing Vice President, answered the gamers' questions on Twitter. He confirmed that in order to avoid piracy the physical copy of the disk will bear only a partial installation of the game. Gamers who bought a legit copy can simply go to their Steam...