Amy is a survival horror game where the player controls the woman Lana as she attempts to escort the 8-year old autistic girl Amy out of a city overrun with creatures and military. At the start of the game they are together in a train as Lana escorts her to a hospital after she is busted out of a shady research facility. The train suddenly derails and they end up in a dark and hostile environment. The game is played from a third-person perspective and the main goal is to make sure Lana keeps Amy out of harm's way. The creatures send out an infection, but Amy has an immunizing aura that prevents Lana from being infected as long as she keeps close. Therefore she walks around holding the girl's hand most of the game and they often need to sneak past hazards together. Lana is however also able to take out enemies with melee combat mechanics using sticks and crowbars, but in many situations that is not an option due to the number of opponents. Weapons also degrade over time. When Lana lets go of Amy, the infection gradually sets in and it causes the contamination sensor on her back to turn from green to yellow and red. It turns her skin pale and renders her vision hazy, but at certain points in the game it is necessary to sneak past creatures who then think she is one of their own.
As Amy's survival is vital for Lana, in many locations she is able to make her hide in closets or other spots when danger is lurking. The options to hide appear automatically when a viable location is nearby. Lana can also hide together with the girl or just by herself. All other control over Amy is also indirect. Lana can ask her to stay in a fixed place, call her to come over, make her turn on a lamp, or ask her to interact with an object in the environment. Amy has to hack into computers, crawl through small grates to access rooms, stand on elevators, and push buttons. There are also locks that can only be opened by collecting a specific DNA sample. These interactions are used extensively for environment-based puzzles. Later in the game Amy gets access to two psychic powers she can call upon; sending out a bubble that knocks down an opponent and a field that silences everything inside. These are activated by having Amy draw a glyph at specific locations around levels. The game consists of six chapters and saving is done automatically through checkpoints.