Online learning has emerged as a critical alternative to traditional face-to-face education, especially in the context of a rapidly digitalising society. This study aimed to investigate students’ perceptions of their academic performance and mental health in the context of online learning versus face-to-face learning utilising the COVID-19 period when learning modalities shifted significantly, to identify the advantages and challenges associated with each modality. Methods: A cross-sectional study was developed. A survey was distributed exclusively to undergraduate pharmacy students who underwent studies before and during COVID-19. Statistical analyses, including t-tests and correlation analyses, were performed to compare face-to-face and online learning environments and to ex- plore relationships between demographic factors, academic performance, and mental health. Key Findings: A total of 70 responses were included in the study. Students significantly favored face-to-face learning over online learning in terms of attentiveness, grades, practical assessments, resource access, communication, and motivation. They reported higher anxiety and worry during online classes and a greater need for mental health resources. Older students and those born overseas adapted better to online learning, while males and those speaking a different language at home faced more challenges. Strong positive correlations were observed between perceived grades and teacher support in face-to face settings, and between anxiety levels and perceived support during online learning. Conclusions: This study sheds light on students’ perceptions of their academic performance and mental health in the transition from face-to-face classes to online learning. Our findings highlight the importance of understanding students’ diverse perceptions and experiences in different learning environments. Educational institutions and educators should tailor their learning approaches and support mechanisms to meet the varying perceptions of students. This involves maintaining the quality and effectiveness of face-to-face learning settings and creating more engaging, supportive, and enriching online learning environments that aligns with students’ perceptions.