Mysterious disappearances have been occurring throughout the South Pacific at the mysterious resort on Austral Island. Honey Kisaragi catches wind of and decides to investigate by sneaking onto the island with help from Danbei Hayami and the player character (an associate of Danbei's son Seiji) who comes on the request to find a family's daughter named Mizue.
The player arrives on Austral Island and befriends Miku Fujiwara. After spending some time on the island, the player finds a dark secret hidden in the shadows when Miku was being kidnapped by thugs. The player is later brought to Mizue who had been transformed into a kaijin by Panther Claw. Cutie Honey then appears after this revelation and fights the mutated Mizue off ending her life.
The player finds out from Honey that Austral Island is really a place that Panther Claw uses to create kaijin from guests of exceptional worth. With Miku among the kidnapped guests, the player teams up with Honey to rescue her and stop Panther Claw. They find out that the fortune teller Damia is actually the one who seeks out potential recruits by using her stand and a chip in her prop mask to find them and having the Panthers abduct them later. Honey fights against Damia in her kaijin form Needle Panther and defeats her.
With more investigations such as the player finding his pass card, the player and Honey eventually confront Panther Claw's leader Sister Jill. Miku is rescued before she can be converted into a kaijin while Honey fights Jill. Ultimately, Honey is victorious, ending Panther Claw's scheme. The player while unable to tell his clients any good news about Mizue, he is happy that Miku is safe.
Cutie Honey FX contains elements of a visual novel and dating simulation with the player's exploration and communication between other characters being automatic with the only actions the player really does is clicking on areas, keeping up with dialogue, and picking from various choices throughout the game. Some of the characters the player encounters include Miku Fujiwara, a guest who is one of the first people that the player encounters. During battle scenes, the player assists Honey by empowering her attacks and guiding her attacks to certain areas. At a certain part, the player even chooses what form Honey can assume.
This is the first Cutie Honey game that was made with an original story. New forms called Fantasy Knight Honey armed with a broadsword, Wrestler Honey uses acrobatic wrestling techniques, and Commando Honey who uses a pistol are used for this game along with combat animations built for the game. The costume used for the game is based on the outfit Honey wore in the original Cutie Honey anime. The plot was later used for the light novel Cutie Honey Vol. 1.
- Cutie Honey's Fantasy Knight Honey form resembles Lina Inverse from the Slayers franchise.