The type of decision dependent uncertainties (DDUs) imposes a great challenge in decision making, while existing methodologies are not sufficient to support many real practices. In this paper, we present a systematic study to handle this challenge in two-stage robust optimization~(RO). Our main contributions include three sophisticated variants of column-and-constraint generation method to exactly compute DDU-based two-stage RO. By a novel application of core concepts of linear programming, we provide rigorous analyses on their computational behaviors. Interestingly, in terms of the iteration complexity of those algorithms, DDU-based two-stage RO is not more demanding than its decision independent uncertainty (DIU) based counterpart. It is worth highlighting a counterintuitive discovery that converting a DIU set into a DDU set by making use of “deep knowledge” and then computing the resulting DDU-based formulation may lead to a significant improvement. Indeed, as shown in this paper, in addition to capturing the actual dependence existing in the real world, DDU is a powerful and flexible tool to represent and leverage analytical properties or simply domain expertise to achieve a strong solution capacity. So, we believe it will open a new direction to solve large-scale DIU- or DDU-based RO. Other important results include basic structural properties for two-stage RO, an approximation scheme to deal with mixed integer recourse, and a couple of enhancement techniques for the developed algorithms, as well as an organized numerical study to help us appreciate all algorithms and enhancement techniques’ computational performances.