Nexus

The Nexus is the heart of the Strogg hivemind and its destruction is the primary goal in Quake 4. Only the Makron has ever laid eyes on the Nexus as stated in the final level. If and when the Nexus is destroyed, communication to the Strogg army will be disrupted, bringing their forces into disarray and giving the invading humans a real chance to achieve victory. There were two operations to disable the Nexus, Advantage, which failed due to being based on bad intel, and Last Hope, which was a complete success.

The Nexus Core itself appears to be a huge brain resting on a large spinal column (much like a real human brain), protected by a powerful force field. This force field can be disabled by destroying the power cell above the Nexus. With the force field down, the player can directly shoot the Nexus for a very short period, damaging it and ultimately destroy it in a bath of blood and guts. The Nexus has no weapons but it can spawn Strogg troops including Iron Maidens, Gladiators and Heavy Tanks to name a few to kill any trespassers before they do any damage.

Operation: Advantage
Due to the heavy defences of the Nexus, at first, an attempt was made to cut it off the Strogg forces by disabling a Tetranode, a massive data router transmitting the Nexus' signals to a part of said forces. Success would have meant the defeat of the Strogg in that area, and would have probably been followed by other similar operations. The plan involved four squads assaulting the facility which housed the Tetranode. Each squad had an EMP bomb, and at least one squad had to get into position and activate the EMP, destroying the Tetranode. Rhino Squad was the only squad to get deep enough, but a passing Harvester destroyed the EMP, rendering the plan a failure. A backup plan was attempted, involving a marine, Matthew Kane, to destroy the Tetranode by shutting down the coolant system. Although Kane managed to reach the control room for the coolant, he was stopped by two Stream Protectors and the Makron himself. After a brief confrontation, Kane was defeated which led to his partial stroggification and the failure of Operation: Advantage. It's revealed to the player that the EMP would have been too weak to defeat the Tetranode.

Operation: Last Hope
Last Hope involved a direct assault on the Nexus, which was heavily guarded from outside and in. In order to even get close to the Nexus Core, the security stations atop the the three towers that surround the Core had to be activated. Kane, with his Strogg implants was the only being who could activate these stations.

Kane infiltrated each tower, Data Storage, Data Processing and Data Networking and made his way to the rooftops, activating the laser beams and then traveling between each tower via a tram rail. During his descent of Processing, Kane came face to face with the Guardian. The Guardian returned on Kane's ascent of the Networking tower where it caused havoc by damaging the tower. Despite the Guardians attacks, Kane reached the top of the third tower where he confronted the Guardian in a boss battle.

Kane activated the final laser beam, allowing a link between the Networking Tower and the Nexus Core. Since only a Strogg could use the teleporter, Kane had to continue and complete the operation on his own.

After navigating the Nexus Core, confronting the toughest defense line yet, Kane reached the Nexus where he fought the Makron, this time to the death. After killing the Makron, the Nexus rose from the floor, allowing Kane to destroy it. Although itself is not posing any danger to Kane, but it was guarded by lots of Stroggs. Despite that, Kane destroyed the Nexus, completing Last Hope, making it exponentially easier in finishing the nightmare once and for all.

Aftermath
In the Strogg storyline, the destruction of the Nexus is the latest event and what happens next is unknown. After getting back to the ship, Kane is given a new mission, which is also unknown, but is implied to somehow involve the/a Makron. There is no word about a new Strogg-related Quake, because John Carmack has revealed that the new Quake, using the id Tech 6 engine (used to power the newest Doom), is going to be horror- and fantasy-styled in the spirit of the original Quake rather than continuing the alien timeline. However, despite these comments, the newest Quake game was instead revealed to be a multiplayer-only deathmatch shooter, Quake: Champions, which combines stylistic elements of the Lovecraftian original Quake with the industrial sci-fi Quake II/4, as well as incorporating bits and pieces of other id Software properties, such as Doom and even Wolfenstein. It remains unknown whether there will be a new sequel to the original Quake or if that project was cancelled entirely in favour of Quake: Champions.