Story related and cannot be missed.
This achievement will unlock after defeating Azmodan, talking to Tyrael in town, and then taking the portal to Act 4.
Note: this solution assumes that you started your character in this version of the game and played through story mode in your own game (not in someone else's multiplayer game). If you transferred a character over from the original version of Diablo III or played in games hosted by someone else, it's possible to miss story related quests and not get credit for this achievement upon moving to Act 4.