Stoppard takes two very minor, but crucial, characters from Hamlet and focuses on them, thus inverting the famous tragedy by giving Shakespeare's main characters minor, walk-on parts, and central roles to these two insignificant would-be bearers of assassinaton orders.
The title is a direct quote from Shakespeare's play - Act V,ii, 350 - when the Ambassador announces that they are dead - and by now, so is almost everyone else, bloodily and visibly. The deaths of Rosencrantz and Guildenstern in Hamlet are interesting in two respects: everyone else is murdered on stage - even the King, if we consider the Players' re-enactment; the deaths of R & G occur off it, announced abruptly and not described. This is the only murder Hamlet commits (or in this case, orders, by altering Claudius's letter) without an agony of conscience - see (V,ii,57-60) when he tells Horatio they deserved all they got.
Stoppard plays chiefly with the idea that characters not visible on the stage must be doing, saying and thinking something - in this case playing word and logic games, and flipping coins in the wings of the main action. They are 'on-stage' only when they are 'off-stage' in the main play, except for a few short scenes when the dramatic events of both plays coincide.
This is a play partly about plays, and Rosencrantz and Guildenstern remain unable to change the action (Hamlet's, but basically Shakespeare's) or change their fate, passive and ineffectual in an absurd play-world where the scene changes abruptly, and where, despite their debates, they have no actual free will to intervene in or alter events. In Hamlet, the two courtiers have no personalities, and act merely as ciphers for Claudius's orders. Stoppard develops them as figures, but not as personalities: they are almost interchangeable, frequently getting their own names muddled, and portrayed as virtual clowns existing in a seemingly irrational, random world beyond their understanding. They engage in pseudo-philosophical arguments, frequently uttering significant truths with implications for themselves and their imminent deaths, but they lose the thread of the implications in the ambiguity (and the absurdity) of the language.
A play can provide answers - a neat plot which has a logic, and an obvious outcome. Real life and real death do not - but then, neither does the play-world if one is basically a bit-player and the 'victim' of other characters and, ultimately, of the playwright. As did Shakespeare, Stoppard leaves the hapless heroes to die off-stage - we expect them to be killed, and they aren't, at least not in front of us. They exist, but as fictional characters, 'alive' only for the play's duration, their 'off-stage' 'life' as fictional as the rest.