Chronic hepatitis B (CHB) is a global health challenge and remains treated with long-term nucleos(t)ide analog (NA) therapy. Nevertheless, NA therapy alone rarely results in HBsAg clearance, the ultimate goal of a cure of function. Pegylated interferon (PEG-IFN) has been examined as a switch or adjunct to HBsAgol treatment to increase treatment response, particularly to achieve HBsAg loss and seroconversion. This systematic review evaluates the efficacy of PEG-IFN for various CHB patients. Databases such as PubMed, Scopus, and Embase were searched for a systematic literature review (SLR). 13 studies were considered eligible and included PEG-IFN add-on or switch studies in CHB patients. A content analysis was used to synthesise findings. The findings show that NA monotherapy was less effective than PEG-IFN add therapy in HBeAg-negative patients. PEG-IFN add-on treatment led to a 28% decline in HBsAg levels compared to NA monotherapy, which did have a significant decrease. HBsAg clearance was also observed in 10% of patients receiving PEG-IFN add-on therapy but none in patients on NA monotherapy. The analysis also showed that 37.4% of patients could reach HBsAg clearance while receiving PEG-IFN add-on therapy, whereas only 1.9% were within the NA monotherapy group. PEG IFN combination therapy is superior to PEG IFN monotherapy in treating CHB patients, especially to the extent that it avoids the possibility of diminishing response. However, further research is needed to select more patients who are more optimal for treatment and longer durations.