You must enter the Twilight Sepulcher and return the Skeleton Key of Nocturnal to its proper resting place. Be aware that you cannot take followers with you when you enter the Sepulcher.
The completion of this quest will remove the Skeleton Key, an unbreakable pick, from your inventory permanently, so you might want to delay this for a while if there is anything in the game that you would like to do involving lockpicking which you so far have not been able to.
Approach the Nightingale Sentinel (Gallus) and speak with him. After exhausting all inquiries, you’ll have the option to search Nystrom’s remains nearby to recover his journal and some other useful items.
Once done, make your way through the tunnel behind him and kill two hostile Nightingale Sentinels you will encounter. After that descend the steps and go through the hole behind the fire pit and continue. Descend some more steps, but be wary of the switch on the floor that will trigger a trap as well as alert the nearby Nightingale Sentinel of your presence. Kill the last Sentinel and go through the door behind it.
In this section, you must keep yourself to the darkened areas as you make your way through the room, as exposing yourself to the light will quickly drain your health. You should also be careful of tripwires on the floor in here as well.
When you get through the next set of doors, follow the path down to the statue of Nocturnal and use both chains hidden behind the torches to open the door. Move along the trap-ridden path that will lead you to the door to the inner sanctum.
If you want you can open a master skill locked door using the Skeleton Key on the left side of this path before reaching the Inner Sanctum door. There are skill books within this room, but you will have to fight two more Sentinels to get it.
If you’re not interested, just proceed through the door to the Inner Sanctum and continue to follow the path again until you come to a well. Examine the skeletal remains of Anders, the thief mentioned in Nystrom’s Journal. A cutscene will begin, and the floor of the well descends to reveal a room with three doors (all closed), and a lock at your feet that requires the Skeleton Key.
Place the key in the slot and Nocturnal herself will appear, comment on your actions, and then depart. You are told to speak to Karliah, who has now joined you inside the Sepulcher. She explains that you can now choose to become one of three types of agent, each with its own unique gift:
Agent of Shadow (Crescent Moon) – Use this power to be invisible for 2 minutes when sneaking.
Agent of Subterfuge (Half Moon) – Use this power to cause all nearby enemies to fight each other for 30 seconds.
Agent of Strife (Full Moon) – Use this power to invoke a powerful life-drain effect.
WARNING: There is a glitch in the dialogue with Nocturnal in which Karliah despawns immediately, preventing you from completing the quest. To avoid this, as soon as Nocturnal begins to speak, use [Wait] for an hour and Karliah should reappear. You should then be able to complete the quest. To be safe, speak to Karliah the instant after Nocturnal finishes speaking so she doesn’t despawn again.
Be aware that brushing against any of the moon symbols will be taken as you making your choice. You can choose again, but only after a period of 24 hours has passed. You can now return to Nightingale Hall and use it as a home if you wish. Karliah will also dwell there.
There is now a short scene where Gallus appears and speaks to Karliah. He offers you the praise that Nocturnal did not, and tells Karliah that they will see each other again when her contract with Nocturnal is fulfilled (i.e., she dies). Travel through any of the shimmering portals to return to the entrance. If you look behind you, what was once the start of the Pilgrim’s Path is now a portal leading to the Twilight Sepulcher Inner Sanctum.
You have completed this quest and restored honour to the Thieves Guild. You are now ready to take your place as its new leader. You can continue to receive jobs yourself from Vex and Delvin.