The study aimed to provide estimates on current polysubstance use among adolescents in Tonga and Vanuatu. Cross-sectional and national school health survey data were analyzed from 5028 adolescents (mean age 15.4 years) in Tonga and Vanuatu in 2016-2017. Polysubstance use was defined as currently using two or three substances of tobacco, alcohol, and cannabis. Results indicate that 72.9% of students reported zero current substance use, 14.5% single current substance use, and 12.6% current polysubstance use (2 or 3 types of substance use). In the adjusted multinational logistic regression analysis factors associated with current single and polysubstance included older adolescents (15-18 years or older), male sex, bullied, passive smoking, high psychological distress, and low peer support, whereby the associations with current polysubstance use were stronger than with current single substance use. In addition, parental tobacco use was associated with single substance use, and school truancy and frequent soft drink consumption (≥3 times/day) were associated with current polysubstance use, and high parental support was negatively associated with polysubstance use. More than one in ten of the participating students engaged in current polysubstance use. Several factors associated with current single and polysubstance use were found which can help in designing intervention strategies.