Polymerase Chain Reaction (PCR) is one of the most common technologies used in many laboratories to produce millions of copies of targeted nucleic acid under in vitro conditions. However, PCR faces multiple challenges including limited availability of DNA in the sample, high GC contents of the template, low efficiency, and specificity in amplification. Moreover, some DNA fragments are very difficult to amplify due to their secondary structure and high melting temperature requirement. To overcome these challenges, many approaches including the application of PCR additives in PCR mixture; change in instrument design; optimization of PCR system by using the accurate concentration of magnesium ions, primers, and cycle number; enzyme modification; and setting up the new touchdown and nested PCR strategies have been adopted. Although these approaches have enriched the output of PCR, they are not all-purpose and optimization can be case dependent. Nanometer-sized materials (nanomaterials) have offered a possible solution to these problems as these materials have exceptional physio-chemical properties as compared to macroscopic materials. Among these nanomaterials, silicon-based materials, carbon-based materials, semiconductor quantum dots (QDs), and some metals are well-known PCR enhancer. Hence, new PCR has been designed to utilize the unique properties of nanomaterial and is known as nanomaterial-assisted PCR or simply nanoPCR. Results of many studies have shown that the combination of these nanomaterials and biomolecules can mimic the DNA replication process successfully as present in the living organism. In this review, we have discussed the role of these different nanomaterials one by one and also discussed the mechanisms through which these nanomaterials enhance the efficiency of PCR.