In this paper, we perform a theoretical study in order to optimize the sensitivity S n and detection accuracy DA performance parameters of a proposed Silver-based and Graphene enhanced Fiber Optic Surface Plasmon Resonance (FO-SPR) biosensor. Upon simulation utilizing the 4-layer model, it was found that the physical and geometrical parameters of this biosensor such as the metal layer type, addition of a Graphene coating, sensing region length L, core diameter D and thickness of the metal layer d 2 have an effect on the sensor performance parameters and thus need to be optimized. The optimal design was found to be a Silver-based and Graphene enhanced FO-SPR biosensor with L = 10 mm, D = 100 mm and d 2 = 40 nm.