Small and medium-sized enterprises (SMEs) are vital to economic growth and job creation, contributing about 40% of Vietnam’s GDP and 50% of employment. However, a substantial proportion of SMEs fail to survive beyond the first few years of operation. This study examines how critical success factors (CSFs)—categorized as entrepreneurial, organizational, managerial, capital, business support, and business environment factors—impact the sustainability of Vietnamese SMEs. Drawing on a survey of 100 SMEs in Ho Chi Minh City, the research employs confirmatory factor analysis (CFA) and structural equation modeling (SEM) to evaluate the influence of these factors on business sustainability. The results indicate that entrepreneurial characteristics, internal managerial factors, and adaptability to the business environment have significant positive effects on SME sustainability, whereas organizational characteristics, external support, and capital availability show no statistically significant direct impact. The findings suggest that developing internal capabilities, strategic adaptability, and proactive management practices are more crucial for long-term SME survival than size or initial capital alone. The paper discusses these outcomes in light of current literature and provides implications for entrepreneurs and policymakers to foster SME resilience.