Background: Multiple Sclerosis (MS) is a chronic autoimmune neurologic condition that affects adults in the prime of their youth, and it is the leading cause of non-traumatic neurological disability in young and middle-aged adults. From the shock of diagnosis to the unanticipated relapses and the dreaded progression, People living with MS (PwMS) are faced with adversity at every corner. Despite the unpredictability of the MS course, some PwMS cope well but others do not. Resilience could determine how PwMS will mend when faced with such challenges, and it is defined by the ability to adapt to their newfound lifetime change generated by their MS diagnosis and disease course. Depression and anxiety have been linked with increased morbidity and mortality in MS, but research targeting the effects of these mental health issues on resilience remains inadequate. Few studies have showed an association between some personality factors (neuroticism and extraversion) and resilience. While it is understood that social support affects resilience, there is no consensus whether this relationship is direct or affected by other variables, such as anxiety, depression, or personality. Objectives: As the concept of resilience remains understudied in the MS population, the specific aim of this research study was to explore the effect of social support on resilience, as moderated by depression, anxiety, and personality in a sample of MS patients at the first regional multidisciplinary MS center in Beirut, Lebanon. Methods: The sample was a non-probability convenience sample that included 100 patients with confirmed MS, ages above 18 years, and able to communicate in Arabic. Potential participants were excluded if they were experiencing an MS relapse. Data collection tools in Arabic: 14-item Resilience Scale (RS-14), ENRICHD Social Support Instrument, Hopkins Symptoms Checklist-25 items, and the Arab Personality Inventory. The data analysis plan included a preliminary analysis, a description of the sample and instruments, association analysis, and moderation analysis. Results: A sample of 100 participants with MS were recruited, 80% had relapsing remitting MS, 59% were women, mean age 37.47 ± 11.23 years, mean disability score EDSS 2.19 ± 1.98, and almost half of the sample had a history of depression. Resilience was high at 83.61 ± 12.98. The percentage of patients with suicidal ideations in this sample was high at 8%. About 44% of the variability in resilience scores is predicted by social support, depression, and extraversion. Higher social support and extraversion and lower depression scores were associated with higher resilience. The relationship between social support and resilience is moderated by extraversion. Conclusions: Results highlight the need to consistently examine resilience with an anthropological lens that views illness as a concept that is culturally constructed, in addition to a biopsychosocial lens to account for the multifaceted nature of MS.