The title of the play refers to a poem called "To a Mouse, on Turning Her Up In Her Nest With The Plough" by Robert Burns in about 1785. The poor mouse has prepared everything for winter, but a plough destroys her nest. The farmer apologizes to the mouse, as he knows she hasn't enough time left to rebuild and restock before winter comes. She is doomed, due to no fault of her own, and there is nothing the farmer can do to prevent her death from either cold or starvation. Her planning was all for nothing.
So it is for George and Lennie. They have finally worked out, with Candy's help, how to buy their own piece of land and build an existence that is safe and secure. Like the mouse, their plan is shattered by circumstances beyond their control. Lennie is doomed and there is nothing George can do to save him. Their plans, too, come to nothing.