Iron oxide-based magnetic nanoparticles (IONPs) have received remarkable attention in a wide range of applications because of their unique physicochemical properties' inheritance to the nanoscale. Among these nanoparticles (NPs), superparamagnetic iron oxide nanoparticles (SPIONs), as powerful noninvasive NPs, are widely used in nanomedicine applications such as targeted drug/ gene delivery, magnetic separation, cancer therapy, and magnetic resonance imaging (MRI) hyperthermia because of their superparamagnetic activity and remarkable small size. The synthesis of SPIONs and surface modification of these NPs for biological applications is an interesting research topic. These NPs have high magnetic susceptibility, a single magnetic domain, and a controlled magnetic behavior due to the SPION superparamagnetic feature. This review aims to explore the recently developed synthetic routes of SPIONs and show the best parameters to prepare SPIONs using pulsed laser ablation in liquid "PLAL" for biomedical applications. Furthermore, we highlight the properties, coating, and functionalization of SPIONs and their importance for biomedical applications, including targeted drug delivery and cancer therapy. The Fe3O4, or superparamagnetic iron oxide nanoparticles (SPIONs), have received considerable attention in a wide range of applications because of their unique physicochemical properties inherent to the nanoscale. These NPs have gained significant benefits due to their unique characteristics, such as superparamagnetic and small size, biocompatibility, biodegradability, nontoxic, efficiently cleared from the human body through iron metabolism pathways, physicochemical properties, drug conjugation/release, scaled up syntheses, and, hence, optimizing the overall parameters for effective medical performance. Various methods are used to synthesize SPION, such as pulsed laser ablation in liquid "PLAL", gas phase deposition, chemical co-precipitation and hydrothermal synthesis. [ABSTRACT FROM AUTHOR]