Background: Existing guidelines lack clear recommendations for the role of locoregional treatment for the primary tumor in women with stage IV breast cancer. We aimed to compare the effectiveness of locoregional surgery with no surgery of the primary tumour in stage IV breast cancer patients. Methods: Eligible studies were randomized clinical trials (RCTs) that investigated the effect of locoregional surgery versus no surgery of the primary tumour in stage IV breast cancer patients. The primary outcome was overall survival (OS), measured as hazard ratios (HRs). Secondly outcomes included 2-year and 3-year OS, expressed as odds ratios (ORs). Meta-analyses and trial sequential analysis (TSA) were conducted. Quality was evaluated using the GRADE. Results: Data were included from four RCTs involving 767 participants, including 377 who underwent locoregional surgery and 390 who with no surgery. The median follow-up was 28.6 months (95% confidence interval (CI) 24.1 to 33.9). In a meta-analysis of these trials, the low-quality evidence indicated that locoregional surgery versus no surgery did not significantly affect OS (HR = 0.87, 95% CI 0.59 to 1.29, P = 0.490), 2-year OS (OR = 1.23, 0.66 to 2.30, P = 0.510), or 3-year OS (OR = 1.08, 0.94 to 1.25, P = 0.263). TSA showed that more trials were needed before reliable conclusions could be drawn regarding in both 2-year and 3-year OS. Across the subgroup analysis of OS, we found the moderate-quality evidence that locoregional surgery followed by chemotherapy versus chemotherapy alone resulted into a significantly improved survival (HR = 0.65, 95% CI 0.49–0.87, P = 0.004); but no statistically significant difference was identified in term of response to chemotherapy with or without locoregional surgery (HR = 1.06, 95% CI 0.83–1.36, P = 0.632). Conclusions: The current evidence suggests that locoregional surgery followed by chemotherapy, compared with chemotherapy alone, was beneficial for prolonging OS in patients with stage IV breast cancer, but surgery did not impact OS among patients who have responded to chemotherapy.