General term for machines ranging in size from a micrometer (one-thousandth of a millimeter) to a nanometer (one-millionth of a millimeter) using MEMS (Micro Electro Mechanical Systems) technology. An example of a nanomachine would be a protein aggregate resembling the structure of a man-made motor using biomolecules such as DNA, proteins, and resins as parts.

During the Shadow Moses Island Incident, Naomi Hunter injected nanomachines into Solid Snake's body, including a nanomachine to supply and administer adrenalin, nutrients, sugar, Nootropics, and benzedrine; a nanomachine to recharge a communication device's battery; and a nanomachine to infect the body with FOXDIE. Nanomachines also made it possible to restrict the host's actions, such as shooting a gun, and to stimulate the host's muscle fibers using ciliary motility. Four years later, the second-generation nanomachines injected into the body of Raiden, who successfully carried out a solo infiltration into Big Shell, were more advanced and their simultaneous function as network terminals had been further enhanced. The nanomachines also handled tasks such as remotely hacking into terminals and nodes connected to Big Shell's operational support network, communication inside the body, the dynamic creation of hallucinations through intracranial nanomachines, and the checking and remote management of VS (vital signs). The number of people with nanomachines implanted had also increased, and almost everyone involved with the Patriots or under their direct control had nanomachines implanted in their bodies.