Higher Education (HE) in Cambodia has relied on a conventional teaching and learning approach; however, this was disrupted by the closure of HEI in 2020 due to the Covid-19 pandemic and the move to online learning. This has resulted in major changes to HE in Cambodia. Therefore, the purpose of this thesis is to explore the implementation conditions experimented by early adopters of Hybrid Teaching and Learning Environment (HTLE) in Cambodian Higher Education, taking into account the changes related to the situation created by the Covid-19 crisis. This research also evaluates from the perspective of lecturers and students the effects of the hybrid teaching and learning environment on students’ 21st-century skills. These skills are called 7Cs including Critical thinking and problem solving; Creativity and innovation; Collaboration, teamwork, and leadership; Cross-cultural understanding; Communications, information, and media literacy; Computing and ICT literacy; Career and learning self-reliance. To identify and describe the HTLE learning design, it adopted the questionnaire from the European research project HY-SUP. There were 20 Cambodian lecturers identified as early adopters from 6 higher education institutions participating in this research using online semi-structured interviews from June to September 2020. A categorical analysis was applied to teachers' discourses. One hundred six students from 9 lecturers also participated through online questionnaires to express their perspectives on the effects of HTLE on 21st-century learning skills development. Results discussed in the light of a systemic model indicated that the main implementation conditions were related to lecturers’ characteristics, such as technological knowledge, engagement, intrinsic and extrinsic motivations, openness to innovation, and selfconfidence in HTLE even though they received little support or no support from their institutions. Other conditions were related to the profile of students, home learning facilities, and profile of the university. The Covid-19 crisis appears to be an event that favours the deployment of HTLE according to them. The result also indicated that most of the lecturers (N=20) agreed HTLE positively affects 21st-century learning skills. Moreover, according to students' opinions (N=106), HTLE seems to impact applying technology effectively and becoming self-directed learners positively. However, students disagreed that HTLE can improve problem-solving, access and evaluation of information, improve collaboration, critical thinking, and working in diverse teams. This thesis could contribute to re-design teaching and learning in the post Covid-19 in Cambodian higher education.