The increasing occurrence of infectious diseases caused by antimicrobial resistance organisms urged the necessity to develop more potent, selective, and safe antimicrobial agents. The unique magnetic and tunable properties of iron oxide nanoparticles (IONPs) make them a promising candidate for different theragnostic applications, including antimicrobial agents. Though IONPs act as a nonspecific antimicrobial agent, their antimicrobial activities are directly or indirectly linked with their synthesis methods, synthesizing precursors, size, shapes, concentration, and surface modifications. Alteration of these parameters could accelerate or decelerate the production of reactive oxygen species (ROS). An increase in ROS role production disrupts bacterial cell walls, cell membranes, alters major biomolecules (e.g., lipids, proteins, nucleic acids), and affects metabolic processes (e.g., Krebs cycle, fatty acid synthesis, ATP synthesis, glycolysis, and mitophagy). In this review, we will investigate the antibacterial activity of bare and surface-modified IONPs and the influence of physiochemical parameters on their antibacterial activity. Additionally, we will report the potential mechanism of IONPs' action in driving this antimicrobial activity.