To investigate the determinants of resilience phenotype in aging, operationalized as the maintenance of cognitive, physical, and psychological health in very old individuals (80+), we investigated the structure and interrelated impact of the main resilience-enhancing factors, which are usually studied in separate research fields. Participants were older adults without dementia recruited for the fifth wave of the InveCe.Ab population-based cohort study (aged 83-87 years). Multidimensional evaluation comprised blood sampling, social and lifestyle survey, geriatric and neuropsychological assessment. We classified resilient individuals as displaying normal cognition, functional independence, and mental health. First, we performed exploratory factor analysis (EFA) to examine the underlying structure of the relevant cognitive, lifestyle, physical, and psychological resilience-enhancing factors. The factors obtained were included as predictors of the resilience phenotype in the logistic regression model, controlling for sociodemographic and cumulative exposure to physical and psychosocial stressors, including COVID-19 infection. Among the 404 enrolled participants, 153 (38%) exhibited the resilience phenotype. EFA resulted in the identification of 6 factors (59% of variance): cognitive reserve, affective reserve, insecure attachment, current lifestyle, physical reserve, and avoidant attachment. Among these factors, cognitive reserve, affective reserve, and current lifestyle significantly and independently predicted resilience status, controlling for cumulative exposure to age-related stressors and COVID-19 infection. Our findings showed that, even in very old age, both early and late life modifiable factors affect individuals' ability to adapt to the aging process, thus confirming the importance of a life-course approach to improve health outcomes in the aged population.