<p>Zinc-based bimetallic nanoparticles (Zn-BMNPs), formed by combining zinc with a secondary metal such as silver, copper, gold, or manganese, offer unique physicochemical and biological properties that surpass those of their monometallic counterparts. This review critically examines two decades of research on Zn-BMNPs, covering synthesis strategies (chemical, green, and microbial), structural characterization, and diverse biomedical activities including antimicrobial, anticancer, antioxidant, and anti-inflammatory effects. Comparative analyses reveal that Zn-BMNPs consistently demonstrate superior efficacy in inhibiting bacterial and fungal pathogens, inducing cancer cell apoptosis, scavenging free radicals, and modulating inflammatory responses, often at lower doses than monometallic systems. Mechanistic insights highlight the role of synergistic ion release, enhanced redox activity, and improved stability. However, significant challenges such as scalability, reproducibility, insufficient toxicological profiling, and lack of rigorous benchmarking against monometallic analogs remain. We identify critical knowledge gaps in mechanistic understanding and propose future directions focused on advanced surface engineering, including stealth polymers, targeting ligands, and stimuli-responsive coatings to improve site-specific delivery and therapeutic precision. By integrating sustainable synthesis methods with multifunctional design, Zn-BMNPs have the potential to become a cornerstone in next-generation nanomedicine.</p>