Background Working from Home (WFH) can have an impact on personal and organizational performance, productivity, health, and well-being. Objective The objective of the study was to investigate working from home over six months using the Ecological Momentary Assessment app (mEMA) with a series of surveys/scales to obtain self-reported information about participants’ well-being. Methods 72 participants enrolled in the study with a completion rate of 63%. Participants were provide with Garmin smartwatches paired with the mEMA which notified them when their surveys were each available. The Computer Workstation Checklist (CWC) was administered monthly. The E-Work Life Scale (EWL) and Flourishing Scales were administered weekly. The Comfort Visual Analogue Scale (C-VAS) and the Joint Pain Homunculus/Pain Visual Analogue Scale (JPH/P-VAS) were administered daily. Results Results suggest that Millennials and Generation Z participants who do have a designated home office and who take three daily breaks or less are most likely to experience increased life satisfaction when working from home. Pain discomfort decreases the probability of experiencing life satisfaction for four groups of participants except those who take three breaks or less. On the other hand, having less flexible work hours adversely impacts the probability of self-reporting life satisfaction only for those who on average take four or more daily breaks while working from home. Conclusion The study highlights the complex interplay of factors affecting remote workers’ well-being. Work flexibility, work-life balance, and stress management emerge as crucial elements in promoting positive well-being outcomes for those working from home. The findings suggest that tailored approaches may be necessary to support different subgroups of remote workers.