Globalization influenced by the development of science and technology has brought the world into the era of industrial revolution 4.0. It led to an unstable and confusing situation, which implies the emergence of VUCA (Volatility, Uncertainty, Complexity, Ambiguity) conditions. VUCA created the term Irregular Warfare as a new form of war, which is defined as a violent struggle between state and non-state actors to gain legitimate influence on the people relevant in the form of terrorist attacks, subversion, and rebellion or separatism. Irregular Warfare in Indonesia is known as a non-military threat, which must be faced by state institutions outside the defense sector as the main element. This study aims to develop a non-military defense strategy in dealing with non-military threats through the collaboration between the ministry of defense with ministries/agencies and local governments as the main elements under the mandate of the defense law. This study used qualitative research methods and phenomenological descriptive-analytical design and supported by relevant theories such as; strategy theory and synergy theory. This study indicates that the synergy of the ministry of defense with the ministries/agencies and local governments is significant in realizing a reliable national defense system.