As Industrial Control Systems (ICSs) increasingly adopt cloud–edge collaborative architectures, they face escalating risks from complex cross-domain cyber threats. To address this challenge, we propose a novel threat assessment framework specifically designed for cloud–edge-integrated ICSs. Our approach systematically identifies and evaluates security risks across cyber and physical boundaries by building a structured dataset of ICS assets, attack entry points, techniques, and impacts. We introduce a unique set of evaluation indicators spanning four key dimensions—system modules, attack paths, attack methods, and potential impacts—providing a holistic view of cyber threats. Through simulation experiments on a representative ICS scenario inspired by real-world attacks, we demonstrate the framework’s effectiveness in detecting vulnerabilities and quantifying security posture improvements. Our results underscore the framework’s practical utility in guiding targeted defense strategies and its potential to advance research on cloud–edge ICS security. This work not only fills gaps in the existing methodologies but also provides new insights and tools applicable to sectors such as smart grids, intelligent manufacturing, and critical infrastructure protection.