Purpose: The present study aims to examine the effects of work from home (WFH) on employees' performance and wellbeing during the second wave of pandemic and to find out the effects of institutional head's support as mediating variables and employees' self-efficacy as moderating variables on employees' performance and wellbeing during WFH. Design/methodology/approach: A quantitative approach with causal comparative research design was adopted to collect the data from the respondents. The participants of the study were 586 teachers from public and private universities of Karachi, Pakistan, who were teaching from home during the second wave of pandemic, selected randomly from the population. An adopted questionnaire was used to collect data which consists of six parts. Findings: Results found the positive significant effects of WFH on teachers' social wellbeing, negative significant effects on teachers' performance, their physical and mental wellbeing. No significant effects of WFH were found on teachers' financial wellbeing. The study also found that head's support plays a partially mediating significant role in the relationship between WFH and job performance, and social wellbeing, while no mediation on physical, social and financial wellbeing was found. Moderating effects of teachers' self-efficacy exist between the relationship of WFH and teachers' job performance, mental wellbeing and social wellbeing, while no effects exist between the relationship of WFH and teachers' physical and financial wellbeing. Originality/value: The new research model will contribute significantly to education practitioners' knowledge, especially the government of Pakistan, which needs to measure their work from home policy's effectiveness during the pandemic.