- Vayne's first name is Shauna.
- Like many other hunters of the supernatural, Vayne's character concept is inspired by
, the protagonist from Bram Stoker's 1897 novel, Dracula.
- Vayne's name and past are possible references to DC Comics character .
- Vayne may also be a reference to the DC Comics character , due to the the similarities between their weapons and pasts.
- Vayne bears some resemblance to the main character from the game .
- Vayne's Silver Bolts, is a reference to the belief that supernatural creatures, particularly , are vulnerable to weapons made from silver.
- Vayne is the only champion to currently have a defense rating of 10.
- Vayne's dance is inspired by the Gun Kata . A side-by-side comparison can be seen here.
- Vayne is the first champion who shares her title with a skill name, followed by Zyra.
- Vayne is the first champion to always have a quote play out when learning a skill.
- Vayne's quote "On wings of night." is similar to Shyvana's quote "On wings of fury."
- Vayne's quote when using her ultimate, "The die is cast" is a reference to Julius' Caesar phrase "Alea Iacta Est". 
- In the background of Classic Vayne's splash art, there is a tombstone labeled "URF" in reference to Urf, the Manatee, and Yorick's shovel.
- Vindicator Vayne is likely a reference to the from the Underworld film series.
- Vayne in her Aristocrat skin is wearing clothing.
- Heartseeker Vayne is a tribute to Valentine's Day.
- There is speculation that Vayne is secretly investigating the activities of LeBlanc and the Black Rose organization.
Art SpotlightVayne Art Spotlight(06:37)