Diablo 4: Vessel of Hatred introduces a plethora of fresh content to the loot-driven dungeon crawler, encompassing a new region, mercenaries, and Runewords. Runewords are forged when two runes are combined in an item equipped with two sockets, yielding potent bonuses. These novel items are exclusively accessible with the expansion, offering a wide array of choices once unlocked.
Runewords are unlocked during the main Vessel of Hatred questline, specifically during the Madman, Crowned quest where you must converse with Ormus in the Council Chambers. Post your discussion, you'll receive an overview of the Runewords mechanics and an initial set of Runes to commence experimentation. Runewords do not start dropping as loot until this quest is completed, urging you to prioritize the Vessel of Hatred campaign, or at least this mission.
For a Runeword to function, two halves must be merged into a single item. This necessitates an item capable of holding two sockets, such as a two-handed weapon, pants, chest, or helm. There are ritual Runes and invocation Runes. Ritual Runes generate offerings through specific tasks, for instance, the Yul Rune grants 50 offerings each time a skill with a cooldown is used. Invocation runes trigger a special ability upon accumulating enough offerings, which might range from reducing active cooldowns to activating an ability from another class. Combining one of each Rune in a single item results in a Runeword. You can activate only two Runewords simultaneously but can unsocket them at a Jeweler to make adjustments or swap Runes.
Currently, farming for specific Runes is not feasible, but general Rune farming is. Runes can drop from any loot source but appear more frequently from activities yielding large chests as rewards. Infernal Hordes and summoned bosses typically drop at least one, if not several, and activities like Helltides can also yield them. The best spot for farming them is the Undercity in Kurast.
Utilizing Tributes that explicitly state they will drop Runes rewards you with Runes upon completing an Undercity run, provided you attain attunement level 1 by clearing enough enemies across the three floors before the boss fight. These also drop randomly, with Tree of Whispers caches being the most consistent and abundant source. Once you have four identical Runes, you can reroll them at the Jeweler for a random Rune, with a fair chance of it being of higher rarity than the Runes you rolled. Exercise caution when rerolling Runes, as they are essential for crafting specific Mythic Uniques. You can consult the Jeweler to identify which Runes are required for which Mythic, allowing you to save them.
