Melanin nanoparticles (MNPs) have attracted growing attention in biomedical fields due to their wide bioavailability, high biocompatibility, biodegradability, and multifunctionality. Key features of MNPs are broad-spectrum light absorption, high drug-loading capacity, near-infrared light-triggered drug release and reactive oxygen species generation, efficient hepatobiliary, renal clearance, and superior binding affinity towards metal ions that enhance MNPs’ traceability in magnetic resonance imaging (MRI). Despite challenges such as agglomeration in time, lack of extraction standardization, and a limited number of animal and clinical studies, the strong photothermal conversion and reactive species production abilities of MNPs make them effective photosensitizers and photothermal agents, while their dual capability for molecular binding and metal chelation positions them as promising agents for theranostic applications. This review provides a comprehensive overview of MNPs, covering their structural features, manufacturing methods and associated limitations, and recent advances in their physicochemical characterization. Special focus is given to MRI-guided biomedical applications, including drug delivery, photothermal therapy, and photodynamic therapy, along with critical challenges related to the clinical translation and commercialization of MNP-based platforms. By consolidating recent advances, this review highlights key structure–function relationships that underpin emerging melanin-based nano-systems.