Business-to-business (B2B) manufacturing companies are increasingly confronted with transformative trends such as sustainability, digitalization, and servitization. These trends are changing how product portfolios are developed, and how value contributions are assessed, and therefore have disruptive potential. Dealing with these disruptive factors in Product Portfolio Management (PPM) is a largely unexplored topic. This study presents an empirical-qualitative exploration that contributes significantly to the field. The aim is to clarify the extent to which disruptive factors influence the evaluation and shaping of the product portfolio in B2B manufacturing companies. The Gioia method was used to evaluate 21 semi-structured interviews with experts from leading B2B manufacturing companies. Eight overarching challenges in PPM resulting from disruptive factors were identified. Based on the eight overarching challenges and their associated causal relationships, two aggregated dimensions of action were derived: (1) increasing speed and flexibility by using generative artificial intelligence (AI) in a defined PPM process and (2) adjusting the product portfolio evaluation to consider various strategic drivers. These two dimensions of action call for future research to overcome the disruptive factors in PPM.