The MSME sector has made a significant contribution to the development of economy in countries across the world. But empirical evidence worldwide shows that a large percentage of the SMEs fails within a few years of incorporation or remain stagnant and small in size for a long time. Using ‘literature review’ as the methodology, this paper tries to do a systematic analysis of the causes of sickness that SMEs all over the world, specifically those in the emerging markets, have reported. It has been found that apart from individual characteristics of the entrepreneurs and external macro economic factors, the major causes of sickness of MSME include poor infrastructure and lack of market focus, financial disorder, lack of managerial skill and lack of good governance. Subsequently, a comparative analysis was also done with the SMEs in the developed nations like those in the OECD countries who had faced similar issues earlier, and during the last two decades have taken some improvement measures to address their sustainability challenges. Important recommendations for improved business sustainability include development of entrepreneurial skill, internationalisation, partnership and collaboration, education and innovation and government intervention. The paper also discusses the applicability of similar measures in Indian context.