The game originally started off as a short tutorial game called Helena for Agustín Cordes' other game which he was working on, Asylum. It was going to be presented as "an Edgar-Allen-Poe-style short story of a game".

The game Serena was developed as a sort of kind gesture to games journalist and adventure game fan Serena Nelson, who had been at the center of a furious outing by Replay Games' president, Paul Trowe. Agustín Cordes, who designed the game and worked at Replay Games, was a bystander of the event and wanted to show respect to Serena by naming the game after her, as a way of providing a positive reaction to a negative event.