Surface plasmonic resonance (SPR) has been a corner stone for approaching single molecular detection due to its high-sensitivity capability and simple detection mechanism, and has brought major advancements in biomedicine and life science technology. Over decades, the successful integration of SPR with versatile techniques has been demonstrated. However, several crucial limitations have hindered this technique for practical applications, such as long detection time and low overall sensitivity. This review aims to provide a comprehensive summary of existing approaches in enhancing the performance of SPR sensors based on “passive” and “active” methods. Firstly, passive enhancement is discussed from a material aspect, including signal amplification tags and modifications of conventional substrates. Then, the focus is on the most popular active enhancement methods including electrokinetic, optical, magnetic, and acoustic manipulations that are summarized with highlights on their advantageous features and ability to concentrate target molecules at the detection sites. Lastly, prospects and future development directions for developing SPR sensing towards a more practical, single molecular detection technique in the next generation are discussed. This review hopes to inspire researchers’ interests in developing SPR-related technology with more innovative and influential ideas.