Surface plasmon resonance (SPR) comprises several surface-sensitive techniques that enable the trace and ultra-trace detection of various analytes through affinity pairing. Although enabling label-free, sensitive detection and real-time monitoring, several issues remain to be addressed, such as poor stability, non-specific adsorption and the loss of operational activity of biomolecules. In this review, the progress over sensor modification, immobilization techniques and novel 2D nanomaterials, gold nanostructures and magnetic nanoparticles for signal amplification is discussed. The advantages and disadvantages of each design strategy will be provided together with some of the recent achievements.