The widespread availability of tobacco products, coupled with aggressive marketing tactics, poses a considerable threat to the youth by encouraging tobacco use initiation. From 2018 to 2022, the prevalence of overall tobacco product use, combustible tobacco product use, cigarettes, e-cigarettes, and the use of smokeless tobacco products have increased among 13-15 y.o. students in San Marino. The increase was larger among girls than boys. To assess the prevalence of nicotine and tobacco use among 13-15 y.o. students in San Marino, data from the latest two national Global Youth Tobacco Surveys (GYTS) were analyzed. In 2022, 13.7% of students (11.5 of boys and 16.2% of girls) used any tobacco product compared with 7.4% of students (7.3% of boys and 7.4% of girls) in 2018. E-cigarettes have become the most popular product among the youth followed by cigarettes. The current use of e-cigarettes has increased from 8.9% (9.9% of boys and 7.6% of girls) in 2018 to 16.1% (14.6% of boys and 17.8% of girls) in 2022. The use of smokeless tobacco products has also increased, especially among boys. In 2022, 1.6% of students (2.4% of boys and 0.7% of girls) currently used smokeless tobacco compared to 0.6% (0.7% of boys and 0.4% of girls) in 2018. There is an urgent need to strengthen the implementation of tobacco control policies in line with the WHO Framework Convention on Tobacco Control. Robust and comprehensive tobacco control policies that cover novel and emerging nicotine and tobacco products have to be adopted and appropriately enforced.