The Tangled Web side quest in Hogwarts Legacy becomes available during the Stop Ranrok and Rookwood main objective. Travel to the Three Broomsticks in Hogsmeade. Once there, speak with Crispin Dunne next to the fireplace. He’ll tell you about a hamlet that is overrun with spiders and how he hasn’t heard from his friend Mary who lives there.
Exit Hogsmeade and head for Aranshire which is southeast of town past the train station. When you arrive at the hamlet you’ll need to clear out the spiders occupying the town square. You’ll then want to head into the house closest to the Floo Flame to find Mary. Interact with her web covered body to find a note then exit the house.
Head to the back of Mary’s house and enter her cellar. Work your way through the cellar then climb down a ladder into an underground cavern to find the nest. Destroy all 12 egg sacs while taking down all of the spiders that stand in your way. When that’s done, head to the main room of the cavern to face another group of spiders who will open a new path for you. Follow this new path to reach the Insatiable Spider. Defeat her and her minions. You’ll also want to make sure to grab the collection chest here as well. Return to Crispin and give him the news to complete the quest. You’ll receive the Sinister Oddities Shelf conjuration as a reward.