Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a multifactorial inflammatory condition that remains poorly understood. Over the past decade, we have witnessed impressive scientific advancements that have allowed us to better understand the molecular and cellular mechanisms that underlie the inflammatory processes in mucosal diseases including asthma, allergic rhinitis, and CRSwNP. Objective The present review aims to summarize and highlight the most recent scientific advancements that have enriched our understanding of CRSwNP. Methods A comprehensive review of the available literature on the use of new scientific techniques in CRSwNP was performed. We evaluated the most recent evidence from studies using animal models, cell cultures, and genome sequencing techniques and their impact on our understanding of CRSwNP pathophysiology. Results Our understanding of CRSwNP has rapidly progressed with the development of newer scientific techniques to interrogate various pathways involved in its pathogenesis. Animal models remain powerful tools and have elucidated the mechanisms behind esinophilic inflammation in CRSwNP; however, animal models reproducing polyp formation are relatively sparse. 3D cell cultures have significant potential to better dissect the cellular interactions with the sinonasal epithelium and other cell types in CRS. Additionally, some groups are starting to utilize single-cell RNA sequencing to investigate RNA expression in individual cells with high resolution and on a genomic scale. Conclusion These emerging scientific technologies represent outstanding opportunities to identify and develop more targeted therapeutics for different pathways that lead to CRSwNP. An additional understanding of these mechanisms will be critical for developing future therapies for CRSwNP.