We investigated sex differences in 473,260 adolescents’ aspirations to work in things-oriented (e.g., mechanic), people-oriented (e.g., nurse), and STEM (e.g., mathematician) careers across 80 countries and economic regions using the 2018 Programme for International Student Assessment (PISA). We analyzed student career aspirations in combination with student achievement in mathematics, reading, and science, as well as parental occupations and family wealth. In each country and region, more boys than girls aspired to a things-oriented or STEM occupation and more girls than boys to a people-oriented occupation. These sex differences were larger in countries with a higher level of women’s empowerment. We explain this counter-intuitive finding through the indirect effect of wealth. Women’s empowerment is associated with relatively high levels of national wealth and this wealth allows more students to aspire to occupations they are intrinsically interested in. Implications for better understanding the sources of sex differences in career aspirations and associated policy are discussed.