The purpose of this study is to review the literature and compare the outcomes of lymph node dissection (LND), or lymphadenectomy, versus no lymphadenectomy (no LND) and extended lymphadenectomy (ELND) versus standard lymphadenectomy (SLND) in various commonly diagnosed solid malignancies with high mortality rates in the United States. We searched for randomized controlled trials involving high-mortality solid tumors, including prostate, bladder, lung, breast, colorectal, pancreas, liver, endometrial, ovarian, and esophageal cancers, in Medline, Embase, and Cochrane Library. The primary endpoint was overall survival, and secondary endpoints included progression-free survival and complications. We identified 4,436 studies in a database search. Of the 43 eligible clinical trials in this study, 31 studies (72.1%) compared LND versus no LND, and the remaining 12 studies (27.9%) compared ELND versus SLND. None of the studies in either comparative group showed a significant difference in overall or recurrence-free survival, with the exception of one study in breast cancer, where ELND was associated with improved overall survival (HR 1.15, 95% CI 1.01-1.30; p = 0.03) compared to SLND. However, ELND across several cancers may be associated with increased risks of complications compared to SLND. The results from this study could help with counseling patients regarding the role of LND in staging of the disease, rather than improving the outcomes. Despite the heterogeneity of the cancers included in this study, the commonality of the lack of survival benefit of LND in most cancers identifies an opportunity for further understanding and the need for additional research on the impact of metastasis to lymph nodes on cancer outcomes.