Quality of life (QoL) in cardiac surgery patients is increasingly recognized as a critical outcome, influenced by biopsychosocial variables. This study aims to explore the associations between preoperative QoL and various psychological and biomedical variables in patients undergoing cardiac surgery. The study includes cross-sectional baseline data from 204 cardiac surgery patients in two distinct cardiac surgery samples: Data collection for the PSY-HEART I trial (coronary artery bypass grafting) was conducted from 2011 to 2015, while data for the ValvEx (valvular surgery) trial were collected between 2020 and 2022. We assessed psychological variables, such as illness beliefs and expectations, alongside biomedical variables, including body mass index, EuroSCORE II, and C-reactive protein levels. Data analysis involved partial correlation Gaussian Graphical Models (GGM) and Directed Acyclic Graphs (DAGs) to identify key nodes and pathways affecting QoL. The resulting GGM was estimated to be rather sparse (38 of 136 possible edges were present) and the case-drop bootstrap node stability estimates ranged from sufficient (CS-Coefficient Bridge Expected Influence = 0.28) to good (CS-Coefficient Expected Influence = 0.51). Our analyses revealed strong associations between psychological variables and preoperative QoL, with current and expected illness-related disability being central to the network. Medical variables showed weaker connections to QoL. The DAG indicated that expected disability influenced current disability and preoperative QoL, suggesting that preoperative expectations may be crucial for postoperative outcomes. This study underscores the importance of psychological variables, particularly illness perceptions and expectations, in determining QoL in cardiac surgery patients. Targeting these variables through preoperative interventions may enhance postoperative recovery and QoL, advocating for a biopsychosocial approach in cardiac surgery care.