(1) Food security. Not many people talk about the fragile system that supports our ability to stay nourished. At the same time, "nourishment" is relative -- we're getting fatter, it's unclear whether industrial agriculture is sustainable, etc.
(2) Social inequality, lack of social mobility, etc. This is something that will have a major impact on our way of life in the coming decades if it continues. Look at Europe and the US to see how fragile and unstable our societies are (and how much worse it's getting).
(3) AI. OK, everyone is talking about it, but I don't worry about it in the context of AI destroying the world, but rather how problem #2 above and #3 mean fewer jobs, more inequality, etc. At this rate, we will not become a society where our subservient AI-robot-slaves do our work for us while every human is enlightened and self-actualized. Instead, automation will drive the cost of labour down and thus cause more inequality in the decades to come. Of course people will continue working -- this defines them, and whatever meagre salary they make is necessary to survive.
(4) Our inability as a species to accept that galactic space exploration will probably be painful, slow, and require generations of space travlers to sacrifice their egos and lives to enable their ancestors to arrive at the destination they set out for. Maybe I'm pessimistic but there won't be "warp speed" and if that's the case, then space travel and galactic colonization will require re-defining what it means to be a human race -- it'll be more akin (and more extreme) to the way colonists visited the Americas -- they gave up their families, communication with the "Old World", etc. to start a new life. Now imagine these same colonists would set off but accept that they would die on the journey, as would their children, and their grandchildren, and only their grand-children would arrive at the destination to maybe prosper, or maybe die... We need to accept that this might be what galactic colonization looks like. I don't think we're ready for this as a race/species/society.