Objectives: In 2021, Thailand experienced its fourth and fifth waves of COVID-19, overwhelming the nation’s public health system. The significant gap between health resources and the demand for services from patients was one of the primary challenges in responding to the catastrophic COVID-19 pandemic. Hospitals were inundated with a surge in new patients, leading to a growing backlog of individuals suffering delayed care or even rejection from the healthcare system. To tackle this issue, strategies such as “outpatient self-isolation” (SI), “home-based isolation” (HI), and “community-based isolation” (CI) were implemented to stabilize COVID-19 cases with mild to moderate symptoms. This review aimed to explore the experiences in the management of COVID-19 care in patients with mild to moderate symptoms and identify challenges after the initial response of the Thailand health system to the pandemic. Methods: This study was conducted during the Delta pandemic (June–November 2021) and the Omicron pandemic (December 2021–15 March 2022). We present the lessons learned from the management of the HI system based on experiences gained at a university hospital, which provided remote professional-to-patient support during the pandemic. The study involved retrospective data from electronic medical records and qualitative analysis of responses provided during the pandemic using the HI system. Results: Data from a total of 2704 and 1912 participants were included in the analysis. The vast majority of patients were assigned to HI immediately after being diagnosed with COVID-19. This system facilitated remote consultations, provision of necessary medications, and delivery of survival kits to patients’ homes. Qualitative reviews indicated several key factors that could contribute to successful COVID-19 management under the HI system: (1) effective management and vaccine status, (2) establishment of home isolation using the find-test-trace-isolate-support system, and (3) adherence to home isolation guidelines and system support. Challenges included the digitalization of tools for securing isolation, team preparedness and adequate support system during HI, as well as hospital policies for psychological support for healthcare workers and measures to alleviate their workload. Conclusions: Our investigation suggests that the HI teleconsultation system was an effective approach to managing COVID-19. It allowed for a prompt response to patients’ needs and provided timely access to medical support, particularly for individuals with mild to moderate symptoms.