Newcomb's problem is a thought experiment in decision theory that challenges traditional decision-making strategies by presenting a scenario where a decision-maker must choose between two boxes, one of which may contain a large sum of money. The challenge arises from the idea that the contents of the boxes are determined by a predictor who can accurately predict the decision-maker's choice. This creates a dilemma where traditional strategies like expected utility theory may not provide a clear solution, leading to debate among philosophers and decision theorists.