Economic security, as one of the principal pillars of national security, plays an unparalleled role in the country’s social and economic development as well as in the sustainability of its security. The concept of economic security, within the context of global transformations, pressures arising from economic sanctions, and the necessity of realizing a Resistance Economy, has assumed particular importance and has become a focal point for policymakers. Drawing upon the thought of Ayatollah Khamenei, the present article examines and articulates the principal requirements and obstacles of the economic security strategy of the Islamic Republic of Iran as its central research question. Reducing dependency on imports, developing knowledge-based industries, relying on a Resistance Economy, and emphasizing domestic production are identified as among the most important requirements for achieving economic security. Conversely, factors such as weaknesses in inflation management, failure to develop downstream industries, dependence on oil revenues, and neglect of the principles of the Resistance Economy are presented—within the research hypothesis—as serious challenges to economic security from Ayatollah Khamenei’s perspective. The research method is descriptive-analytical, and data collection was conducted through written sources and the official information portal of Ayatollah Khamenei.