Amid the COVID-19 pandemic, the Philippines shifted to distance learning, later transitioning to hybrid setups with limited face-to-face classes. At the University of Santo Tomas (UST), hybrid learning has become a permanent setup. As this offers flexibility, it also brings challenges to students, as highlighted by related studies. The goal of this study is to assess and analyze behavioral, physical, and macro-ergonomic factors influencing their learning motivation and academic performance. A total of 287 engineering students in UST, using purposive sampling, answered the questionnaire in an online administered survey. Behavioral and ergonomic factors were analyzed using the Partial Least Square-Structural Equation Model (PLS-SEM). Results showed that attendance, student-centered method of teaching, and use of a learning management system positively influence learning motivation, which positively impacts their academic performance. The findings imply that students, academic teachers, and school administrators should be aware of and apply behavioral, physical, and macro-ergonomic concepts to positively influence students’ learning in a hybrid learning environment. As hybrid learning has become a norm in the university, it is essential that behavioral and ergonomic factors are considered to establish an effective learning system as it improves students’ learning motivation and academic performance in a hybrid learning setup.