Bosses are found on Assassination missions. Each boss has a set of lines to "taunt" the Tenno sent to kill them. They often drop mods and resources upon death. Depending on which Boss the player is fighting, Blueprints of Warframes parts and special Weapons parts will often be rewarded upon mission completion.
On the other hand Assassins hunt players in random locations. Their appearance are triggered by various actions done by the player, such as killing a Boss or assisting an opposing Factions in Invasion missions.
All bosses and assassins have a chance to drop an Orokin Cell upon death.
On Tolstoj, Mercury, he will reward the Seer blueprint along with its components, including the Orokin Cells, as all bosses have a chance to drop those. There is also a small chance to reward a Cronus blueprint. On Iliad, Phobos, he instead rewards blueprints and components for the Miter, Trinity and the Twin Gremlins.
- Main article: Councilor Vay Hek
Councilor Vay Hek is the hidden boss located on a secret base on Earth. After defeating him and completing the mission, players will receive a blueprint for either a Hydroid Helmet, Hydroid Chassis or Hydroid Systems. Upon death, Councilor Vay Hek has a chance of dropping Neurodes, Orokin Cell and Argon Crystals.
- Main article: General Sargas Ruk
General Sargas Ruk is the final boss of the Saturn system. He can be found on the mission Tethys. After defeating him and finishing the mission, you receive either Ember Helmet, Chassis or Systems blueprint. Has an increased chance to drop an Orokin Cell upon death.
- Main article: Kela De Thaym
- Main article: Lieutenant Lech Kril
Lieutenant Lech Kril is the final boss of Ceres, and also makes an appearance on Phobos alongside Captain Vor as a dual boss battle on the planet. He can be found on the mission Exta on Ceres and Iliad on Phobos.
On Phobos, he rewards Miter parts and its blueprint, or the Twin Gremlins blueprint. He also drops blueprints for Trinity components. He has two phases, first being Ice and the second Fire, which he will enter after his cryo pack is destroyed four times.
- Main article: Alad V
Alad V is a Corpus boss who resides on Jupiter (replacing J3-Golem). He is accompanied by a robotic pet/guardian, Zanuka, which he built from Warframe parts that he gathered.
Upon completion of his assassination mission, player will receive either the Valkyr Chassis, Helmet, or Systems.
- Main article: Ambulas
Ambulas is the boss of the Pluto system. It can be found on the mission Hades. After defeating it and finishing the mission, you will receive Excalibur Chassis, Helmet, or Systems blueprint. Upon death, Ambulas has a chance of dropping Morphics.
- Main article: Hyena Pack
The Hyena Pack are the final bosses of the Neptune system. They can be found on the mission Psamathe. After defeating them and finishing the mission, you receive either a Loki Helmet, Chassis or Systems blueprint. Upon death, all the Hyenas have a chance of dropping Orokin Cells.
- Main article: Jackal
Jackal is the final boss of the Venus system. It can be found on the mission Fossa. After defeating it and finishing the mission, you have a chance to receive the Rhino Helmet, Chassis, or Systems blueprint.
- Main article: Raptor
The Raptor is a Corpus Boss found in the Europa system in the mission Naamah. After defeating it and finishing the mission, players will receive either the Nova Chassis, Helmet or Systems blueprint. Upon death, Raptor has a chance of dropping Morphics or Control Modules.
- Main article: Phorid
Phorid is an infested boss, found when an infested invasion manages to "Infest" the boss node. After defeating it and finishing the mission, you receive Nyx Helmet, Chassis, or Systems Blueprint. Upon death, Phorid has a chance of dropping rare Resources of the planet he has appeared.
- Main article: Lephantis
Lephantis (previously known as J-2000 Golem) is a massive Infested boss introduced in Update 10. It was originally going to replace (the now-retired) J3-Golem but was moved to the Orokin Derelict tileset instead. Lephantis requires players to craft a special Derelict Assassination key, which requires five Golem Nav Coordinates; items only obtainable though Derelict missions; missions which require regular Nav Coordinates found in normal missions.
Assassins are boss-like NPC's that hunt players in random locations after doing certain things against their Factions, earning their respective Death Marks in the process. In the Stalker's case, he will target players who have defeated one of the regular enemy bosses in the game as "revenge". The Harvester and The Grustrag Three will target the player when they aid the opposing faction in an Invasion mission. They usually drop rare resources and exclusive weapons when defeated.
- Main article: The Grustrag Three
- Main article: Harvester
The Harvester (ingame: Zanuka Hunter) is a gray-colored Zanuka proxy controlled by Alad V. During missions, it will attack one targeted Tenno until either the Tenno or the Harvester dies. It appears rarely, in a manner similar to the Stalker.
- Main article: Stalker