Background: Synchronous lateral pelvic lymph node (LPLN) involvement occurs in a significant number of patients with rectal cancer. The aim of this study is to determine the rate of LPLN metastases in rectal cancer patients with LPLN suspicious for metastases (LPLNSM) on pretreatment imaging, treated with neoadjuvant chemoradiotherapy (nCRT). Additionally, the influence of LPLN responsiveness to nCRT as determined by post-nCRT restaging scan was investigated. Methods: A systematic review was conducted to identify studies on patients with author-defined LPLNSM that reported the pathological outcomes after total mesorectal excision (TME) with lateral pelvic lymph node dissection (LPLD). MEDLINE, EMBASE, Web of Science and the Cochrane Library were searched. The primary outcome was the percentage of pathologically confirmed LPLN metastases. Results: A total of 462 patients from eleven studies were identified. The number of pathologically confirmed LPLN metastases in 361 patients that underwent uni- or bilateral LPLD ranged from 21.9 to 61.1%. The LPLD resulted in pathologically confirmed metastases in a range from 0 to 20.4% of patients with responsive LPLNSM and in a range from 25.0 to 83.3% of patients with persistent nodes. However, radiologic cutoff criteria for the evaluation of LPLN differed between studies. Conclusions: In a large number of patients with LPLNSM on initial imaging, metastatic LPLN are present after nCRT and surgical treatment. Even in LPLN that are considered responsive on restaging, significant rates of pathologically confirmed metastases are reported.