Southeast Asia (SEA), which has borne the brunt of some of the most severe natural disasters in the past decade, has unfortunately, been largely under-represented in the world literature on disaster mental health. This article describes cultural factors that may inform the design and conduct of disaster-related mental health psychosocial support (MHPSS) interventions. Specifically, it discusses cultural nuances in emotional expression, shame, power distance, collectivism, and spiritual beliefs and their implications on providing post-disaster psychosocial interventions. It describes the MHPSS interventions implemented in the region using the Johns Hopkins Perspectives Model of Disaster Mental Health categories of resistance, resilience and recovery. Given the challenges on the delivery of MHPSS, there is a need for evidence-based interventions and to ensure that disaster responders in SEA understand the cultural factors that impact the delivery of MHPSS interventions.