Designing complex, socio-technical, cyber-physical systems has become increasingly challenging in recent years. Interdependencies between engineering domains can lead to emergent behavior that is difficult to predict and manage. The recent shift toward model-based design has demonstrated significant advantages for minimizing these challenges. Further, the early identification of safety and security design weaknesses in safety-critical systems leads to reduced redesign costs in later design phases. As a result, this article contributes the Multidisciplinary Early Design Risk Assessment Framework for early combined safety and security assessment based on interdisciplinary dependency models of a system. The focus is on factors contributing to the estimation of the probabilities of successful attacks on system components. The Zero Trust paradigm is applied in which all humans, hardware, and processes interacting with the system are considered to pose a security risk. A calculation of security-related probability estimates is presented which is dependent on the current global security environment. Subsequently, security and safety probability estimates are combined to present an overall safety-security risk calculation using hybrid safety-security trees. The risk values help designers assess the loss of specific key components and safety functions. The methodology is demonstrated with a case study of a spent fuel pool cooling system in a nuclear reactor. The results of the case study show that the risk of losing one key system component doubles when combining security and safety compared to only assessing safety events. This paper is based on a paper presented at CIE 2020.