The outbreak of the COVID-19 pandemic has brought forward an unprecedented situation, which has forced the educational institutes worldwide to use a propriety "online only" model for teaching and learning. Teachers have been compelled to deliver lectures online using some form of an online delivery platform. In this dilemma situation with the closure of the educational institutes, one of the very basic necessities is to ensure quality features of e-learning systems that are being used for the purpose of education delivery, particularly from the students' perspective. The objective of this study was to identify factors affecting pharmacy students' satisfaction in Vietnam during the COVID 19 pandemic. A cross-sectional survey of a consecutive sample of 1612 valid responses from students who have been in distance learning at Hanoi University of Pharmacy has been conducted. An integrated model with three main dimensions had been developed: learner's characteristics; instructor's characteristics; system, and technology. Data were collected in the field on both online and offline platforms using the questionnaire of 39 items to investigate the critical factors affecting learners' satisfaction in e-learning. The reliability of the questionnaire was measured using Cronbach's alpha on this data. Descriptive statistics, factor analysis, and multiple regression analysis were employed for data analysis. Out of 2491 questionnaires distributed, 1612 questionnaires were completed (respond rate 64.7%). The results revealed that perceived usefulness, perceived ease of use, system and technical dimension and instructors' characteristics are the critical factors affecting learners' perceived satisfaction. The perceived usefulness of the students was the most important factor affecting overall satisfaction (beta coefficient = 0.610). Multiple regression analysis yielded the four main factors explaining 59.9% of total satisfaction. The findings revealed how to improve learners' satisfaction and further strengthen their e-learning implementation. The interventional solutions on students' characteristics, instructors' characteristics and system & technical dimension should be considered and implemented to improve the quality of e-learning and students' satisfaction at Hanoi University of Pharmacy.