Methicillin-resistant Staphylococcus aureus (MRSA) has evolved vast antibiotic resistance. These strains contain numerous virulence factors facilitating the development of severe infections. Considering the costs, side effects, and time duration needed for the synthesis of novel drugs, seeking efficient alternative approaches for the eradication of drug-resistant bacterial agents seems to be an unmet requirement. Nickel nanoparticles (NiNPs) have been applied as prognostic and therapeutic cheap agents to various aspects of biomedical sciences. Their antibacterial effects are exerted via the disruption of the cell membrane, the deformation of proteins, and the inhibition of DNA replication. NiNPs proper traits include high-level chemical stability and binding affinity, ferromagnetic properties, ecofriendliness, and cost-effectiveness. They have outlined pleomorphic and cubic structures. The combined application of NiNPs with CuO, ZnO, and CdO has enhanced their anti-MRSA effects. The NiNPs at an approximate size of around 50 nm have exerted efficient anti-MRSA effects, particularly at higher concentrations. NiNPs have conferred higher antibacterial effects against MRSA than other nosocomial bacterial pathogens. The application of green synthesis and low-cost materials such as albumin and chitosan enhance the efficacy of NPs for therapeutic purposes.