Endgame is one play of the Theatre of the Absurd in which, at least in my opinion, the themes are made relatively clear. This is not necessarily to say that Beckett's usual message about the meaningless nature of life is not present here. But the situation that unfolds is a metaphor for a recognizable reality experienced by people throughout the world, even if it's stated here in an exaggerated and especially trenchant form.
A bare stage is the setting, in which two men, who are both disabled in different ways, are arguing with each other, while two other people are sitting in trash cans. Hamm is physically disabled and blind; Clov cannot sit down; and Hamm's parents, Negg and Nell, are living in the trash cans. The world seems to have been depopulated apart from these four people. Obviously this is a parable of the restrictive nature of real life, in which people go through the motions and act as if they are doing things of consequence, but it's actually all without meaning. It is as if humanity has shrunk down to these pathetic specimens who, like the objects of a satire, are an over-emphatic representation of some negative and unforgivingly absurd quality.
How or why is this different, if indeed it is, from other modernist works? In my view, Ionesco's plays, for example, are more openly without a definite message of any kind, other than the assertion that life is without purpose. Brecht, on the other hand, clearly has a collectivist (as Ayn Rand would put it) social agenda. Beckett straddles the fence between these two extremes, most obviously so in Endgame. Despite the fantasy-apocalypse of its setting, it is more concrete in its metaphorical reality than Waiting for Godot. One can even judge the situation of Nagg and Nell as an uncomfortable picture of the neglect and abuse of elderly parents. And the work has characteristics of meta-fiction: Hamm and Clov posture for the audience with a semi-awareness that they are actors in a stage work. Endgame, moreover, partakes of the dystopian genre as well, serving as a warning (though Beckett would probably have strenuously denied any such purposeful message) that humanity can degenerate into this skeletal remnant if it proceeds on its current course.