
So... I busted. And learned a lot. This is a card you have to read really careful:
While you can take this card out of pure greed that's not what I did. I played it in The Web of Dreams and turned out fine. Not Jacqueline Fine-fine, because she exists no more, but fine enough to continue playing after I was defeated.
Playing The Great Work - and other XP greed cards - is inefficient in The Dream-Eaters, because it does proc less often than in normal campaigns.
There are two common ways to approach this card:
1) Just slot it into any deck that can take it to get more XP, having a solid enough deck to prevent being defeated.
2) Count on being defeated at some point. That requires making sure your deck can handle being a Homunculus. I.e., Spell cards with abilities as your main way of interacting with the game. This approach can also be viable if you are playing a campaign with lots of potential extra weaknesses or maybe if you are playing cards with exile (I am awaiting an answer from Alex Werner).
Since I fell in 2) with my run, I essentially only lost 1 and the token fishing when using Wither and Sixth Sense.
What I really mourned was loss of power with Drain Essence. Why is that? Because the wording on the Homunculus is "You get +2 skill value while resolving abilities on Spell cards." It doesn't work with [Drain Essence] (/card/10094), because the effect that you resolve when playing it is not an ability, according to arkhamdb.com So I wondered why, when abilities mainly exist on cards in play, did they not phrase it so it says "You get +2 skill value while resolving abilities on Spell ASSETS."? My best guess is because cards like Bind Monster and the taboo-ed Power Word exist. Too bad for Drain Essence, still...
On the plus side, I was defeated in the scenario that would have added a story weakness into my deck - and ignored that one with a grin.
ANOTHER surprising find (heh) was that when you are transformed, the scenario doesn't necessarily end for you. How come, you ask? It's a bit of a rare case, but if you are playing an investigator with less than 6 (aka the Homunculus's) health or sanity and then would be defeated on point, The Great Work acts very similar to Cheat Death. Since - according to arkhamdb.com -, the trigger for the investigator replacement happens before the impact of being defeated on the game state, you would now have an investigator with, say, 5 damage on them, but with 6 health instead of 5. And that means you'll live! Note that, like Cheat Death, the ability does not replace being defeated, it just sneaks an effect into the game before it actually happens.
The list of eligible investigators for this to happen is longer than I actually expected: Amina Zidane, "Ashcan" Pete, Daisy Walker, Gloria Goldberg, Hank Samson, Luke Robinson, Mark Harrigan, Michael McGlen, Rita Young, Roland Banks, Sefina Rousseau, Silas Marsh, Sister Mary, and Tony Morgan.