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You shouldn't be missing much, if anything, at your depth. Look into optimizing your teams, try for teams that can handle Realm Instability 5. You'll want to be able to beat bosses at that difficulty, you get lots of extra keys if you beat Nether Bosses at RI 5.
Also make sure you are unlocking extra realms from your projects, and battle the creature masters for mastery and mastery traits.
If you unlock more classes, you get more rewards for the Goblet of Trials, even though you will have to reroll to get specializations you have built teams for if you go nuts unlocking them like I did. I still feel it's worth it, but it is a consideration.
Finally, place Nethermancer Ned in your castle if you haven't already. He sells you special trait materials you can use in your team, based on which Nether Bosses you've beaten, with more trait materials after beating them a second and third time. On the 4th time you'll get skins for each of the Nether Bosses.
Edit: I mentioned that Gate of the Gods unlocks at 240. I just wanted to add that this is the next major unlock, and beating the Gods lets you summon Avatars with special traits that you can add to your team. You can only have 1 Avatar on a team at a time, and while you can fuse them to a creature, the Avatar must always be the first creature. The game won't let you fuse it as the second, since that would give you the Avatar trait w/o the Avatar race.
The next big unlock after that is Guilds and False Gods, that requires Realm Depth 415 to be beaten, and will allow you to unlock a multi-classing type of system called Anointments. It lets you pick perks from other classes (up to 5) and add them to your current build. Inquisitor, for example, really benefits from Blighted immunity, and Greater Healing and Overheal from Cleric. That ensures his heals always work, no matter what. Since his own abilities scale creature offense based on amount healed, those perks are amazing. Alternatively, you can grab Censure and Divine Strength from Inquisitor to give to Cleric to get that offensive pressure on a Cleric build.
This was super helpful! Thank you. It sounds like I have some work to do. One difficulty I'm running into now is like you said, I unlocked a bunch of classes and don't have optimized teams. But now even my optimized Monk team is getting owned depending on what I run into.
Which reminds me of my question--should I be going hard to upgrade artifacts/etc. all the time? I haven't done a ton on those to optimize my team, mostly just messing around with them occasionally.
Once I get a solid team put together I level their artifacts to max. Artifacts are very powerful.
RI0 is playing without realm instability modifiers active (the default way to play and the one that rewards vastly fewer rewards).
Your wiping enemies faster than with no realm modifiers is possible due to poor trait interactions and random enemies. The one thing that playing with no modifiers has over playing with modifiers is realms tend to have trait composition that works by design. Realm modifiers can make for some really weak or really strong combinations.
Also note that some of those modifiers are no longer in actual use.
Just wanted to say thank you for this amazingly helpful and informative post. I wasn't sure what was the next major milestone in my grinding and this was quite useful.