Background Septic shock (SS) is the most common severe syndrome in the Intensive Care Unit (ICU). Enhancing the monitoring of hemodynamic indexes in SS patients carries huge clinical implications for reducing patient mortality. Recently, pulse indicator continuous cardiac output (PICCO) has been widely used in clinical practice, but its advantages than central venous pressure (CVP) in guiding the treatment of SS patients remains to be refined. Therefore, this study is aimed at assessing the clinical effects of PICCO in the treatment of patients with SS. Methods The authors systematically searched several databases (PubMed, EMBASE, Cochrane Library, and China National Knowledge) between January 2001 and February 2021. When searching for relevant articles, the authors combined the following phrases describing the monitoring group (“pulse indicator continuous cardiac output,” “central venous pressure”) with the disease of interest as well as management (“SS,” “sepsis”). The outcomes were independently assessed by two reviewers who scored the articles for methodological quality using the Cochrane Collaboration's “risk of bias” tool. Forest plots, as well as sensitivity and bias analyses, were carried out for the included articles. The primary outcome measures were length of ICU stay, duration of mechanical ventilation, 28-day mortality, and fluid resuscitation volume. Results Ten studies comprising 350 cases monitored with PICCO and 373 cases monitored with traditional CVP were eventually identified. PICCO-monitored patients were observed to be significantly associated with shorter ICU stay than CVP-monitored patients (MD: −3.04, 95% CI: −4.74 to −1.34, P = 0.0005), shorter time of mechanical ventilation (MD: −1.84, 95% CI: −2.80 to −0.87, P = 0.0002), and lower 28-day mortality (RR: 0.67, 95% CI: 0.48 to 0.94, P = 0.02). The two groups showed no significant difference in subgroup analysis for fluid resuscitation volumes (P > 0.05). Conclusion PICCO monitoring technique can significantly improve the prognosis of SS patients, shorten the time of mechanical ventilation and ICU stay, and reduce the 28-day mortality, which has positive guiding significance for patients with SS. Given the limitations of the quantity and quality of included studies, further research is warranted to verify the conclusions.