Grit is the perseverance and passion for long-term goals, optimism represents an individual’s expectation of a positive outcome in most situations, whereas life satisfaction is a major indicator of well-being. Grit, optimism, and life satisfaction play a role in medical and health science education, as they are associated with academic performance. This cross-sectional study explored the relationship between grit, optimism, and life satisfaction among medical and health sciences students at a Malaysian university using the 12-Item Grit Scale, Life Orientation Test-Revised (LOT-R) scale and Satisfaction with Life Scale (SWLS). Medical students were significantly grittier than optometry students (p = 0.015) and significantly more optimistic than biomedical science students (p = 0.007). Academic performance was significantly correlated with grit (r = 0.135, p = 0.027) and optimism (r = 0.139, p = 0.023). On the other hand, a significant correlation existed between grit and optimism (r = 0.316, p = 0.000) as well as optimism and life satisfaction (r = 0.328, p = 0.000), whereas a correlation was observed between grit and life satisfaction (r = 0.171, p = 0.003). The findings show that interdisciplinary differences in grit and optimism exist and that grit and optimism are related to the academic performance of medical and health sciences students. Grit, optimism, and life satisfaction were interrelated in this study.