Advances in (bio)medicine and technological innovations make it possible to combine high-dimensional, heterogeneous health data to better understand causes of diseases and make them usable for predictive, preventive, and precision medicine. This study aimed to determine views on and expectations of “systems medicine” from the perspective of citizens and patients in six focus group interviews, all transcribed verbatim and content analyzed. A future vision of the use of systems medicine in healthcare served as a stimulus for the discussion. The results show that although certain aspects of systems medicine were seen positive (e.g., use of smart technology, digitalization, and networking in healthcare), the perceived risks dominated. The high degree of technification was perceived as emotionally burdensome (e.g., reduction of people to their data, loss of control, dehumanization). The risk-benefit balance for the use of risk-prediction models for disease events and trajectories was rated as rather negative. There were normative and ethical concerns about unwanted data use, discrimination, and restriction of fundamental rights. These concerns and needs of citizens and patients must be addressed in policy frameworks and health policy implementation strategies to reduce negative emotions and attitudes toward systems medicine and to take advantage of its opportunities.