Background <p>Motor heterogeneity in Parkinson’s disease (PD) reflects the interplay between dopaminergic and nondopaminergic circuits. While dopaminergic therapy restores activity within basal ganglia–cortical motor pathways, residual ON-state motor impairment represents nondopaminergic dysfunction. The determinants of these two components and their relation to quality of life remain incompletely understood.</p> Objective <p>To identify independent clinical correlates of dopaminergic and nondopaminergic motor loads and to assess their combined effects on quality of life in PD.</p> Methods <p>This retrospective study included 688 idiopathic PD patients evaluated with MDS-UPDRS (I–IV), NMSS, FOG-Q, FES-I, VHI, HAM-A, HDRS, and PDQ-39. Dopaminergic motor improvement was defined as Δ (MDS-UPDRS III OFF–ON), and residual nondopaminergic severity as ON-state MDS-UPDRS III. Multivariable regression analyses identified independent predictors and quality-of-life determinants.</p> Results <p>Greater dopaminergic improvement was associated with longer disease duration (β = 1.60, p = 0.010) and higher FOG-Q scores (β = 2.10, p = 0.001). Among NMSS domains, Sleep/Fatigue correlated positively and Mood/Cognition negatively with dopaminergic responsiveness. Residual nondopaminergic motor load was predicted by older age (β = 0.147, p &lt; 0.001), higher FES-I and VHI scores, and NMSS Mood/Cognition and Sexual domains. In quality-of-life models, both nondopaminergic motor load (β = 0.41, p &lt; 0.001) and total non-motor burden (β = 0.87, p &lt; 0.001) were independent determinants of poorer PDQ-39 outcomes.</p> Conclusion <p>Dopaminergic improvement declines with disease progression yet remains modulated by freezing-related responsiveness. Nondopaminergic motor load—shaped by axial, bulbar, and limbic-autonomic features—and overall non-motor burden jointly account for quality-of-life deterioration in PD. Addressing both dopaminergic and nondopaminergic domains is crucial for comprehensive management.</p>