The menisci exert a prominent role in joint stabilization and in the distribution of mechanical loading. Meniscal damage is associated with increased risk of knee OA. The aim of this study was to characterize the synovial membrane and meniscal tissues in patients undergoing arthroscopic partial meniscectomy for meniscal tear and to evaluate association with clinical outcomes. A total of 109 patients were recruited. Demographic and clinical data were collected. Visual Analogic Scale (VAS) measuring pain and Knee injury and Osteoarthritis Outcome Score (KOOS) were recorded at baseline and at 2-years follow-up. Histological and immunohistochemical characterizations were performed on synovial membranes and meniscal tissues. More than half of the patients demonstrated synovial mononuclear cell infiltration and hyperplasia. Synovial fibrosis was present in most of the patients; marked vascularity and CD68 positivity were observed. Inflammation had an impact on both pain and knee symptoms. Patients with synovial inflammation had higher values of pre-operative VAS and inflammation. Higher pre-operative pain was observed in patients with meniscal MMP-13 production. In conclusion, multivariate analysis showed that synovial inflammation was associated with pre-operative total KOOS scores, knee symptoms, and pain. Moreover, meniscal MMP-13 expression was found to be associated with pre-operative pain in multivariate analysis. Thus, targeting inflammation of the synovial membrane and meniscus might reduce clinical symptoms and dysfunction at the time of surgery.