Shirayuki and Zen Wistalia have finally confirmed their romantic feelings for each other, and everyone has resumed their daily lives. Shirayuki remains an apprentice court herbalist at the royal palace of Clarines, and Zen continues his duties alongside his aides. However, their daily routines are disrupted when Crown Prince Izana, Zen’s older brother, receives an invitation from Raji Shenazard, the prince of Tanbarun. The herbalist finds herself ordered to go to Tanbarun for seven days, to build a new friendship with the formerly selfish and haughty ruler who once ordered Shirayuki to become his concubine. Along the way, Shirayuki is bound to run into trouble once again, as she is sought by a mysterious boy named Kazuki, someone she has never met.

Although her name means snow white, Shirayuki is a cheerful, red-haired girl living in the country of Tanbarun who works diligently as an apothecary at her herbal shop. Her life changes drastically when she is noticed by the silly prince of Tanbarun, Prince Raji, who then tries to force her to become his concubine. Unwilling to give up her freedom, Shirayuki cuts her long red hair and escapes into the forest, where she is rescued from Raji by Zen Wistalia, the second prince of a neighboring country, and his two aides. Hoping to repay her debt to the trio someday, Shirayuki sets her sights on pursuing a career as the court herbalist in Zen's country, Clarines. Akagami no Shirayuki-hime depicts Shirayuki's journey toward a new life at the royal palace of Clarines, as well as Zen's endeavor to become a prince worthy of his title. As loyal friendships are forged and deadly enemies formed, Shirayuki and Zen slowly learn to support each other as they walk their own paths.

Otaku siblings Tamotsu and Niwaka Denkigai are shopping in Akihabara when it is overrun by vampiric cosplaying monsters! These creatures, known as Bugged Ones, can possess anyone they bite and soon they begin causing mayhem across the city. As Tamotsu finds himself at the mercy of one of these creatures, he is rescued by the mysterious baseball bat-wielding Matome Mayonaka. Together, they fight through several more encounters with the Bugged Ones, but before long, Tamotsu is fatally wounded protecting Matome. With no other choice, she revives him as a high level Bugged One—just like her! Tamotsu and Matome, along with excitable otaku cosplayer Arisa Ahokainen, make up the group The Electric Mayonnaise and they begin dispatching the Bugged Ones in the only way they know how: by ripping off their clothes and exposing them to sunlight!

Tennomifune Academy is an elite institution for the best and the brightest, with the exception of Class 1-7, the so-called Happiness Class. Each member of the classroom copes with personal misfortunes, and the special class is geared to help them move past their issues and find true happiness. After being accepted into the academy, An Hanakoizumi, Ruri Hibarigaoka, and Botan Kumegawa find themselves placed into the Happiness Class, plagued by dreadful luck, love problems, and bad health respectively. Alongside their classmates, they do their best to overcome the difficulties they are faced with in pursuit of a life filled with joy.