This study aimed to identify and analyze factors associated with a higher risk of 3-year mortality in patients with Parkinson’s disease (PD) within a Romanian cohort, focusing on individuals with more advanced disease stages as indicated by the Hoehn and Yahr scale. We conducted a cross-sectional observational study on 42 patients with PD treated at the Neurology Clinic I, Cluj-Napoca County Emergency Clinical Hospital, between October 2019 and January 2021. All participants were at stages 2.5 or 3 on the Hoehn and Yahr scale at baseline. Various clinical, neuropsychological, and neurophysiological assessments were performed, including evaluations for motor and non-motor symptoms such as anhedonia (via the Snaith-Hamilton Pleasure Scale – SHAPS) and cognitive impairment. The use of antiparkinsonian medications and antidepressants was also recorded. Factors associated with higher mortality risk included a higher anhedonia score (SHAPS > 34; P = 0.03), higher levodopa doses (cutoff = 937.5 mg; P = 0.001), and the administration of mirtazapine (P = 0.04). These findings indicate that non-motor symptoms like anhedonia, along with higher medication doses and specific treatments, play a significant role in influencing mortality risk in advanced PD. This study highlights the multifaceted nature of mortality risk in patients with PD, particularly emphasizing the role of non-motor symptoms and pharmacological treatment. Tailored therapeutic strategies, including closer monitoring of anhedonia and careful management of medication dosages, may be essential in reducing mortality and improving patient outcomes in advanced stages of PD.