System and method for automatic definition and tuning of user segment combinations used for targeted advertisement and marketing. Automated analysis and feedback modules may provide, ad hoc, optimized market segments definitions that maximize the conversion ratio for advertisements. The system and method may optimize of segment data based on a learning-running process built around a data exchange within a real-time bidding (RTB) media exchange system. In identifying qualified combinations for segments on-going loops or iterations may analyze the correlation between the performance of an advertisement or “creative” and user data, based on a set of parameters. As a part of data segmentation, embodiments of the present invention find combinations of parameters that may predict lift. Segment combinations are optimized by, for example combining a segment combination with one or more other segment combinations and/or dividing a segment combination into two or more different combinations.