Improving resistive memory reliability requires understanding some bottlenecks, i.e., control and stability of the memory parameters during endurance cycling and physical degradation that shows up in memories that contain metal oxides. The physical degradation of indium tin oxide/poly[2-methoxy-5-(2′-ethylhexyloxy)-1,4-phenylene vinylene]/aluminum (ITO/MEH-PPV/Al) devices was studied through I–V sweeps and cycle endurance with different compliance currents (IC), in addition to scanning electron microscopy (SEM), energy-dispersive X-Ray spectroscopy (EDS), and Raman spectroscopy. The devices showed a dependence of the conductance quantization G0 in current compliance IC, i.e., the G0 histogram shows different distribution shape after changing IC. After many cycles, the devices presented partial destruction in the active area (physical alteration) followed by memory parameter degradation and finally failing (no commuting anymore). SEM/EDS measurements in the deteriorated region showed that the aluminum electrode was removed and only remnants of the polymer remained. The Raman spectroscopy analyses focused on changes in the polymeric structure caused by the endurance cycle, such as changes in chain planarity, which is related to the band around 966 cm−1 that was shifted to lower wavenumbers (965 cm−1) together with the increase in intensity which indicates less planar conformations when compared to the non-degraded area. Alteration of the conjugation length was evidenced by the contribution around 1581 cm−1. In this case, we can see a shift: of 1581 cm−1 to 1584 cm−1, for the non-degraded area and degraded area, respectively. Both results indicate a decrease in the conjugation length. All these changes show fragmentation of the polymer chain as a result of the endurance cycle.