One of the principal objectives of teaching and learning mathematics, science, and technology (MST) is to produce a digitally-based society, and students are pillars to achieve this fundamental objective in this information age. The study investigated students' attitude in MST education for digitally-based society in the South-West region, Nigeria. A sample of 1,080 from the population of 2,700 was used from six private and six public tertiary institutions in the six states that made up the region. A questionnaire with a reliability coefficient of 0.813 was used to gather research data for analysis. Findings revealed that the students in the South-West geopolitical region had a poor attitude in mathematics, chemistry, physics, and computer science, and there was a poor academic performance in MST education. There was a significant difference between public and private tertiary institutions students' attitude towards MST-related courses. Recommendations on periodical workshops and training of teachers on the innovativeness in the teaching of science-based subjects were made.