Remaining in the realm of physics (physics can't claim to comprehend all of the reality, it is relevant only to objective reality,) it is quantum gravity, as is well known. But in my opinion, quantum gravity can't find a solution if quantum mechanics isn't first understood, a "task" that have been postponed for decades. If there is no "New Physics" (observations that falsifies current theories,) it won't be possible to postpone it further. But the theoretists will probably be more interested in sterile speculations like superstrings, since they allow to publish more often, and thus to earn a living.