Twilight Sparkle is a female Alicorn living in the Equestrian Wasteland, and is very different from what she once was.

Twilight has remained inside Canterlot Missile Base since the Last Lights, unable to leave. This was due to Celestia wanting to "protect her faithful student" at any cost, especially since her former students had either been "corrupted" by other sources (for example Sunset Shimmer joining XCOM) or killed by the Midnight.

Twilight could not bring herself to commit suicide despite her previous actions. She later explains that something had been stopping her inside her own head, as if something was still looking out for her. For this same reason, Twilight seems to fear death after her release.

During the Fallout storyline, every protagonist (Union, Scootaloo, Bramley, Locke, Connor and Kate) come across Canterlot Missile Base and each talk to Twilight. However, all of them (excluding Kate) refuse to release her as each has their own personal grudge against her in some way. Union may never have encountered this Twilight in particular, but his experience with her CHS counterpart and knowledge about her actions in the past severely damaged his thoughts towards her. Scootaloo thinks Twilight is a coward who is afraid to embrace a necessary evil, Bramley considers her an outlaw and says she is where she belongs (locked up), Locke recalls his threat to her 200 years ago, and Connor never trusted her in the first place.

Kate does release Twilight Sparkle, but does so by launching a nuclear missile from beneath Nuketown at Mount Canter. This caused the bunker to fall from it's inside position and pry open, letting Twilight out. As per her agreement, she was willing to travel with Kate and her friends.

Twilight acts very differently when compared to her past self, no longer prioritising lessons of friendship and instead acting as if she is internally deceased to normally-traumatising situations. She obviously exhibits curiosity about the Wasteland as she has no prior experience in it, but also shows she is knowledgeable of Pre-War elements including the remains of inactive Titan (referring to it as the "impending end") and the memorial statues in Everfree City, now buried in dust (stating she isn't proud of her past, and many of those names are her fault). She also comments on Locke, asking him to "move past (their) discretions and focus on the task at hand."

When it comes down to the Omega Platform and Kate's ultimate decision, Twilight states she is incompatible with the mech. Had she been able to, it is likely she would've given her own life rather than let Kate do it. After Kate's sacrifice, Twilight disappears into the Glowing Sea. What becomes of her is unknown, but it is theorised that she survives due to her fighting skill and immunity to radiation. However Twilight could indeed be dead, as the final single-chapter story "Fallout: Apex Forever" sees the two remaining Apex Pilots (Apex and Scootaloo) fighting and before the final stand against the NCR begins, the two Pilots talk of Twilight as if she were dead. As this story is hinted at taking place 10 years after the events of Fallout: Pathfinder, it's entirely possible that Twilight had been killed.