I guess the most fundamental 2 things is climate change, and the societal upheaval likely to result from certain modern technologies.

By climate change, I include patterns in economies, food security, water, migration, wars over resources, population/demographics, public health... that have already started but clearly will intensify.

For technology, I've heard that after the widespread use of the printing press, or the industrial revolution, there were big turbulent changes in society that lasted a century. Some people reckon the modern internet/social media was another such disruptor, and I do agree you can trace a lot of "post-truth", loss of trust in institutions, etc, back to that. AI could make this worse too.

Then, most traditionally rich countries are facing demographic trouble and national debt.

It's not clear how it'll all shake out or when, but it's difficult to see many players being able to afford regular supply missions to Mars in the next phase... lifetimes of people currently alive... we're likely to see less progress than we're used to.