Following the Doctor's trial (TV: The War Games) on Gallifrey, the CIA had him perform tasks for them, offering to amend his original sentence of execution in favour of exile if he would act as a deniable agent in matters they would prefer not to be seen getting publically involved in. The CIA intended for Serena to help the Doctor prevent the Players from interfering with the history of Earth.
Although their initial meeting was hostile, with Serena coolly stating that she was the Doctor's supervisor as he was just a convict on parole while the Doctor regarded her as an assistant he didn't want, Serena had already expressed some admiration for the Doctor, noting that his originally-planned sentence of execution seemed a harsh 'reward' for his role in ending the war games. During their time on Earth, Serena came to understand more about the Doctor and his attachment to the planet, recognising that he left Gallifrey because there was no place on it for someone like him, and grieving the news of the death of Admiral Horatio Nelson even though she had only briefly met him for a few moments.
Serena sacrificed herself to save the Duke of Wellington after she and the Doctor had learned that the Players intended to create a new timeline by assassinating the Duke before the Battle of Waterloo. The Player called Valmont attempted to shoot the Duke at a ball the night before the battle. Serena intercepted the shot, but the musket ball tore through both of her hearts and killed her instantly, which made regeneration impossible. She was buried in a simple grave, marked only by her name, with Wellington assuring the Doctor after the Battle of Waterloo that he would always remember the role he and Serena had played. During a later confrontation with Serena's killer, the Doctor's grief over her death was so intense that he found it easy to allow a duel to take place with Serena's killer despite his usual distate for violence. Once back on Gallifrey, the Doctor refused to go on any more missions for the Agency until certain conditions were met, including an order that Serena's name be placed on the Gallifreyian Honour Roll and that he be allowed to tell her family how she had died. (PROSE: World Game)