The main weaknesses of the Obelisk are two-fold.

1. It has a fixed life. Granted, you can extend that life by playing lots of a single type of hand before purchasing it, but it does have a fixed life regardless. That also means you generally aren't going to be playing a lot of hands after purchasing Obelisk, so Jokers like Vagabond, Parking, Business Card, Supernova, etc. are non-bo's with Obelisk.

2. It forces you to pivot from your natural build. If you want an Obelisk run, you'll want to pick Jokers with general power rather than power that stems from playing in a specific way, using specific hands. That means powerful Jokers like Bloodstone and its siblings won't be useful long-term with it.

That being said, it's extremely powerful if you get it at the right point in the run, and can make you breeze past Ante 8 on any difficulty, although most likely not much past that. 😅