Small and Medium Scale Enterprises (SMEs) have always been faced with various challenges in their journey to attain success. Researchers have identified these challenges to include inadequate funding, inadequate information management and recording keeping, poor infrastructure, lack of managerial skills and many others. With the 2020 pandemic, SMEs had to encounter a new set challenges that seems to threaten the very existence/sustenance of the enterprises. The 2020 pandemic came with attendant negative consequences on both human lives as well as the institutional structures and systems that have been put in place for the functioning of the economy. This study set out to examine the immediate and far-reaching impact that 2020 pandemic had on the activities of SMEs and also measures that could be put in place for the continuous survival of SMEs being the engine and catalyst of growth and development of economies of many countries. The research design for the study is Survey. To guide the study four research questions and three hypotheses were generated. The sample for the study were 101 SMEs located within the Lagos State Metropolis. The instrument for data collection is a questionnaire titled, “Questionnaire on Entrepreneurs Response to Pandemic 2020: Impact on Business Activities of SMEs in Lagos State” which had a Cronbach Alpha coefficient value of 0.60. Data collected from the study was analysed using regression statistical tool on the SPSS version 20. The result from the study revealed that entrepreneurs’ response to 2020 pandemic significantly impacted the product/service package cycle, patronage, profitability and innovative tendency of SMEs. It is recommended that all efforts be geared towards creating an enabling environment for the sustainability of entrepreneurial activities of SMEs in the state as they have been identified as the engine of growth and development of all economies.