There are a variety of factors that pose challenges for start-ups globally. These challenges vary based on the country, region, or economy of operation. Research identified the challenges start-ups face depending on whether start-ups were established in developed or undeveloped countries. However, few research studies have been conducted in Nepal. Hence, the purpose of this study was to examine the top five factors that hindered start-up formation or posed difficulty for the growth of start-ups within Nepal between 2017 to 2020. The primary data was collected using a mixed method using purposive sampling consisting of an in-depth interview followed by a survey with entrepreneurs and experts of the entrepreneurial ecosystem of Nepal. The authors administered an in-depth interview with open-ended questions and then conducted key informant interviews. Throughout the interviews, the five major issues identified as hindering start-ups were human capital, finance, support system, policy, and marketing.