Objective: The study aimed to conduct a comparative analysis of e-commerce adoption in small and me-dium-sized enterprises (SMEs) of Pakistan and Bangladesh in the period following the COVID-19 pandemic. This study aims to observe in detail the significance of e-commerce adoption for small and medium sized enterprises, their abilities to evolve consumer preferences and to dissect the challenges that hinder in the way of e-commerce adoption in Bangladesh and Pakistan. The key focus of this study was to find out how digitisation acts as a moderator to overcome challenges. Research Design & Methods: We based the study on a quantitative design using a structured questionnaire to collect data from 500 SMEs with 250 respondents from each country, Bangladesh and Pakistan. We collected the study sample through a stratified random sampling from key industrial cities in both countries. We analysed the data of the study with SmartPLS version 4.0 to explore the relationship between external factors, need-bead factors, organisational factors, technological factors and e-commerce adoption with digitisation as a moderator. Findings: This study has also examined that market related demands and the access to the technology has significant positive impact on digitisation in both countries. However, company’s resources and cultural factors that are related to the organisational factors have negative impact on digitisation in Bangladesh and Pakistan. The multi-group analysis composed to find the distinguishing factors among two countries, found the impact of all the factors on digitisation. Implications & Recommendations: We observed a crucial role of digitisation in different fields to adopt e-Commerce in SMEs of Pakistan and Bangladesh. This study has been conducted in the time of COVID-19 pandemic, suggests that it should be the top priority of the policymakers to focus more on digitisation to enrich the country’s economic and digital infrastructure. The partnership programs can help both countries improve digitisation on modern standards. Findings suggests combined strategies to boost economic stability of both countries. However, this study has some limitations and future suggestions to entertain the role of artificial intelligence (AI) to examine the adoption of e-Commerce in both countries. Contribution & Value Added: This study has provided a qualified analysis of the drivers of e-commerce adoption in SMEs of Pakistan and Bangladesh in the specific context of the post-COVID-19 pandemic, with digitisation as a moderator. It offers novel insight into the different types of challenges faced by SMEs in both countries and in the transformation of digitisation in the South Asian region.