Purpose <p>Our objective was to assess the perioperative quality of life (QoL) of patients with pancreatic cancer (PC) and accurately capture the complex interactions and causal pointers that contribute to fluctuations.</p> Methods <p>This longitudinal study (October 2024 to March 2025) assessed QoL in patients with PC undergoing potentially curative surgery at four stages: the day of admission (T1), 3–5 days postoperatively (T2), the day of discharge (T3), and 1 month postoperatively (T4). Analysis of variance and cross-lagged panel network (CLPN) analyzed stage differences and dynamic interactions, and centrality calculations mapped important intervention targets between stages.</p> Results <p>Among 277 analyzed patients (89.64% response rate from 309 approached), 66.79% had ductal adenocarcinoma; the remaining cases comprised pancreatic neuroendocrine tumors (11.91%), invasive intraductal papillary mucinous neoplasms (7.58%), solid pseudopapillary tumors (5.42%), and other types (8.3%). QoL differed significantly between stages (<i>P</i> &lt; 0.001). Dimension scores for functioning and global health status declined before gradually improving, whereas symptoms followed an inverse pattern. Nodes with higher bridge-expected influence, out-expected influence, or in-expected influence in each CLPN were targets for clinical care (mainly pain and nausea and vomiting in T1→T2, pain and social functioning in T2→T3, and fatigue and financial difficulties in T3→T4). The accuracy and stability of the CLPN were verified as acceptable.</p> Conclusions <p>The CLPN could precisely identify the interactions and causal connections among QoL dimensions across different stages. It provides anticipatory and prospective guidance for clinical healthcare professionals to enhance holistic care outcomes through early intervention on vital targets that impede dysfunction and symptom exacerbation.</p>