This paper focuses on incorporating individual differences in cognitive processing and semantic markups in the context of adaptive interactive systems. In particular, a semantic Web-based adaptation framework is proposed that enables Web authors to enrich content and functionality of Web environments with semantic markups, which are further processed and reconstructed by an adaptation mechanism based on cognitive factors of users. Main aim of this work is to investigate the added value of personalizing content and functionality of Web environments based on the unique cognitive characteristics of users. Accordingly, a user study has been conducted that entailed a psychometric-based survey for extracting users’ cognitive characteristics, combined with a real usage scenario of an existing commercial Web environment that was enriched with semantic markups and was personalized through different adaptation effects. The initial results obtained provide interesting insights in the design and deployment of adaptive interactive systems based on cognitive factors and semantic markups.