- Major characters
- The Chosen One · Tandi · Joanne Lynette · Dick Richardson · Frank Horrigan · Ken Lee · AHS-9 · Harold
- Dogmeat · John Cassidy · K-9 · Marcus · Myron · Skynet · Sulik
- Major factions
- Enclave · New California Republic
- Minor factions
- Brotherhood of Steel · Hubologists · New Khans · Shi
The game takes place in the year 2241 on the West Coast of what used to be the United States of America, mostly in California and Nevada. Faced with the worst drought on record, the village elders of Arroyo ask the direct descendant of the Vault Dweller, referred to as the Chosen One, to retrieve a Garden of Eden Creation Kit (GECK) for Arroyo.