Appearing only in zero gravity environments, Medusas are best to be avoided. If you get close, they can deliver a devastating melee attack with one of their four limbs. They can also fire projectiles that home in on targets. Therefore, it is better to engage them at long range and kill them before they can attack.
- Most of the time, it is wiser to conserve ammunition and simply maneuver around them.
- Shoot the yellow sacs on their limbs (destroying the main sac will launch two or more projectiles).
The Medusa does not have a specific death scene of its own, instead Isaac or Carver will be split into pieces if the creature kills them with its limb-tentacle.
If Isaac/Carver was hit by a Medusa's homing projectile, whatever part of their bodies hit will be torn off.
- Like the Alien Necromorph, the Snow Beast, and the Nexus, the Medusa also seems to be a Necromorph based on a native lifeform from Tau Volantis.
- If a Medusa finishes off Isaac/Carver with its limb during a Zero-G flight, their bodies will be torn apart while their legs continue to drift off-screen with boosters still active.
- If one kills a Medusa without severing any of its limbs or popping the main sac, its body will twitch violently, causing the main sac to explode. In some occasions, the corpse will mysteriously vanish, most likely due to a glitch.
- The Medusa is similar to the Nest, except it is a mobile form and much more advanced.
- In Greek mythology, Medusa was one of the three Gorgons and was said to be so ugly she could turn anyone she looked at into stone. This name is fitting, given the Medusa's grotesque appearance
- A Medusa is also the name given to the free-swimming stage of Cnidarians such as jellyfish, normally the reproductive stage of a sessile polyp. The Nest's physical appearance seems to support this, as they resemble the stationary polyps.
- It is possible that the Medusa best served their purpose in the oceanic terrain of Tau Volantis during the original Necromorph outbreak and that the ones encountered in the game were ones encased in ice when the planet flash froze. It is unknown how the ones in the zero-g sections of S.C.A.F. storage located at the Alien Machine made their way to those areas, but it is possible that the personnel dumped the back then thought dead carcassess, which adapted well to the gravityless environment.
- Like the Nest encountered in front of CMS Brusilov, it is possible that the Medusa could've been encountered commonly in the orbit of Tau Volantis, had the S.C.A.F. personnel brought the corpses of the Necromorphs for storage similary to other Necromorph specimens.
- Medusas have a similar appearance and behavior to Nemacysts from the Gears of War series.