Essential oils (EOs) have been proved as natural food preservatives because of their effective and wide-spectrum antimicrobial activity. They have been extensively explored for potential applications in food industry, and substantial progresses have been achieved. However well EOs perform in antibacterial tests in vitro, it has generally been found that a higher level of EOs is needed to achieve the same effect in foods. Nevertheless, this unsimilar effect has not been clearly quantified and elaborated, as well as the underlying mechanisms. This review highlights the influence of intrinsic properties (e.g., oils and fats, carbohydrates, proteins, pH, physical structure, water, and salt) and extrinsic factors (e.g., temperature, bacteria characteristics, and packaging in vacuum/gas/air) of food matrix systems on EOs action. Controversy findings and possible mechanism hypotheses are also systematically discussed. Furthermore, the organoleptic aspects of EOs in foods and promising strategies to address this hurdle are reviewed. Finally, some considerations about the EOs safety are presented, as well as the future trends and research prospects of EOs applications in foods. The present review aims to fill the evidenced gap, providing a comprehensive overview about the influence of the intrinsic and extrinsic factors of food matrix systems to efficiently orientate EOs applications.