A very limited list of things that nobody knows (as compiled by yours truly, a very limited human). As you may notice, most of the list treads close to things that may be broadly classed as epistemological questions. Do extend it with your own unknowns. There are some other more comprehensive lists: Science Magazine’s list from 2005. NY Times list from 2003. A New Scientist list from 2005.
What’s the matter with prime numbers. (Reimann Hypothesis)
What are the fundamental constituents of the universe. (see last question)
What is a dimension. How many of it does the universe have.
Can life as we know (so far, it’s just on our little planet) make it to The End. Can it make it beyond The End.
Do numbers have a reality of their own. (GH Hardy: I believe that mathematical reality lies outside us)
Is it possible to know what we can and cannot know.