Set in a crazed, alternate future of Hong Kong, Fear Effect 2: Retro Helix is the prequel to the survival-horror hit Fear Effect. You play as one of four deadly mercenaries on a team that's been commissioned to bring back the kidnapped daughter of a powerful Chinese executive. The action begins with Hana, Glas, and Deke the three main characters from the original game meeting each other for the first time. Soon afterward they meet Rain, a close friend of Hana's. Hana, Glas, and Deke are on separate missions to retrieve three objects, but before long they realize that they're involved in the same deadly plot. The action takes the foursome through Hong Kong, Hell's Kitchen in New York City, the walled city of Xi'an, the lost tomb of the first emperor of China, and in the end, to the mountain island of the immortals, Penglai Shan. Then, after lunch, things really get crazy!

Fear Effect 2: Retro Helix begins in Hong Kong in the year 2048. The player delves into the colorful histories of the original cast of three mercenaries and newcomer Rain Qin, as well as the extraordinary circumstances that brought them together. In the wake of a degenerative global pandemic called EINDS (Environmentally Induced Nucleotides Degeneration Syndrome – pronounced "ends"), theft, murder, and terrorism have become big business. Hana Tsu-Vachel and Rain Qin are freelance operatives, Royce Glas is a washed-up former soldier, and Jacob "Deke" Decourt is a cutthroat assassin. Much of the game's intrigue lies in how these unlikely allies even manage to come together for one cause. From the start, each of them have their own motives, but they soon all become entangled in a sinister plot extending far beyond politics, espionage, or personal survival. The adventure takes players through a futuristic Hong Kong, the formidable walled city of Xi'an, the lost tomb of the first emperor of China, and, finally, into the mountain island of the immortals, Penglai Shan.