This study sought to assess factors associated with quality of life (QoL), and predictive of improvements in QoL over time, in a population-based cohort study. A 4-year longitudinal survey was administered to 2433 individuals at the study baseline; of these, 1828 individuals participated in Wave 2, and 1303 participated in Wave 3. QoL was measured by the Satisfaction with Life Domains Scale. Thirty-two variables were correlated with baseline QoL and together explained 58.2% of the variance. Eleven variables were independent predictors of improvement in QoL over time. Among these variables, social support and stress/coping showed the strongest association with QoL, and neighbourhood characteristics had an additional influence. Multidimensional modelling of a broad spectrum of the factors related to QoL enabled situating mental health and well-being in an ecological system with attendant implications for public health and social policy intervention to facilitate improvement of QoL in the population.