Diablo 4: Vessel of Hatred adds a ton of new content to the loot-driven dungeon crawler, including a new region, mercenaries, and Runewords. Runewords are created when you combine two runes in an item with two sockets, giving you powerful bonuses. These new items are only available if you have the expansion and there is a large variety, giving you plenty of options, once you unlock them.
How to unlock Runewords
You unlock Runewords during the main Vessel of Hatred questline, during the Madman, Crowned quest that takes you to speak to Ormus in the Council Chambers. After speaking to him, you’ll receive a briefing on the Runewords mechanics, and an initial set of Runes to begin experimenting with. Runewords don’t start dropping as loot until you complete this quest, so you try and prioritize getting through the Vessel of Hatred campaign, or at least through this mission.
How Runewords work and where to find more
For a Runeword to work, you need to combine two halves into a single item. This means it needs to be an item that can have two sockets, a two-handed weapon, pants, chest, or helm. There are ritual Runes and invocation Runes. The ritual Runes create offerings by performing a specific task. For example the Yul Rune grants 50 offering each time you use a skill with a cooldown. Invocation runes activate a special ability when enough offering is collected. Sometimes it’s something as simple as reducing any active cooldowns you have, but it can also activate an ability from another class. Combining one of each Rune in a single item creates a Runeword. You can only have two Runewords activated at once, but you can unsocket them at a Jeweler at any time to make changes or swap Runes.
Source: Gamespot Diablo 4: Vessel Of Hatred – How To Unlock And Equip Runewords