A couple of interviews with Hideo Kojima held at Gamescom, as well as the briefing scene shown at the event, shed some light on the story and overall structure of Death Stranding. Warning: the following information may be considered a spoiler.
Kojima stressed that you need to play the game to understand it, but he would try to provide a bit of clarity.
The game takes place in a post-apocalyptic US of the future, which has been devastated by a cataclysmic event caused by ‘Void Outs’, and is now haunted by BTs, monsters from the ‘other side’ that Sam can’t see until he is given a Bridge Baby. This BB is a baby born to a ‘Stillmother’, a braindead mother who is on life-support.
Sam must travel from east to west in order to reconnect the US and re-establish civilization. His end goal is to reach Edge Knot City, which has been taken over by terrorist separatists (The Homo Demens), who are holding future president Amelie (Lindsay Wagner) prisoner. They want to keep the city independent. Meanwhile Sam must reconnect the communication relays (called Cryon terminals) using the necklace as some sort of key (called a Q-PIP) which he received from Die-Hardman.
The briefing takes place inside what looks like the Oval Office, with Amelie talking to Sam as a projection (seeing she is not actually there but on the West Coast as a prisoner of the Homo Demens). While not allowed to leave Edge Knot City, Amelie is free to use the facilities and communicate with Sam. Sam initially refuses to undertake this task, but obviously he eventually sets off on this mission.
There is also a multiplayer aspect that plays into the connection theme of the game, and that apparently will be revealed at Tokyo Game Show next month.
“With Death Stranding I wanted to create something that only I could create.” – Hideo Kojima