Background and Purpose: Oral nicotine products are available in a variety of form factors, ranging from traditional smokeless tobacco (snuff, loose-leaf chewing tobacco, snus) to tobacco leaf-free modern oral nicotine products (pouches, lozenges, tablets). The nicotine dissolution profile of these products influences the timing and extent to which nicotine is released from the product and absorbed into the blood stream through the oral mucosa. The complex interactions between modern oral nicotine pouches (e.g., pH, pouch material) and buccal saliva (composition, flow, pH, enzymes) affect nicotine release into the buccal cavity, which in turn can influence in vivo nicotine absorption, abuse liability potential, and ultimately switching behaviors away from combustible cigarettes. The objective of this study was to conduct a critical evaluation and comparison of in vitro dissolution profiles and associated influential factors of nicotine release associated with different oral nicotine products. Methods: A systematic evaluation of available studies was conducted to compare nicotine dissolution testing data across a range of oral nicotine products, including non-tobacco nicotine pouches and snus pouches. Data were extracted and tabulated for metrics of cumulative and percent of total nicotine release, product characteristics (nicotine strength, pH, surface area, moisture), and in vitro dissolution methodology. Using methodology established by the Food and Drug Administration’s (FDA’s) Center for Drug Evaluation and Research (CDER), the difference factor (f1) and similarity factor (f2) were calculated to compare dissolution profiles within and across oral nicotine product categories. Additionally, available in vivo plasma concentration profiles were qualitatively compared to in vitro nicotine dissolution trends. Results: Results showed that nicotine dissolution behaviors of oral nicotine products are complex. Notable differences in nicotine release rate were observed across a broad range of traditional and modern oral nicotine products. Products with comparable reported nicotine strengths did not necessarily show similar timing and peak nicotine releases. Other product factors, such as pH, surface area, or moisture, were not always reported, but available data did not illustrate obvious associations or trends. One prominent observation, however, was that modern oral nicotine pouch products have the potential for a faster and greater nicotine dose compared to pouched snus products. This enhanced nicotine release was reflected in the in vivo plasma concentration profiles. Conclusions: Dissolution release of nicotine from oral nicotine products performed under in vitro provides insight into product performance and is important for product-to-product comparisons. More importantly, understanding the factors which influence in vitro dissolution profiles of oral nicotine products provides an opportunity for comparison to in vivo pharmacokinetics and development of predictive in vitro-in vivo correlation models.