Mixed ionic-electronic conduction, the simultaneous transport of both electronic and ionic species, is essential for a wide range of established and emerging technologies. During device operation, OMIECs undergo significant structural evolution in response to ion insertion and electrochemical doping, including swelling, phase segregation, and conformational rearrangements, which in turn modulate mixed conduction behavior. These complex structural evolutions stem primarily from the intrinsically heterogeneous morphology of OMIECs, which features a delicate interplay between long-range ordered crystalline and disordered amorphous phases. Each domains playing a critical role in mediating mixed conduction and dynamic response under bias. Calorimetric measurements, therefore, present a vital opportunity. By probing thermal transitions and segmental relaxation, they offer a direct means to investigate the structural evolution of both the crystalline and amorphous phases, addressing a critical knowledge gap in the field. We developed an integrated setup combining a temperature controller, lock-in amplifier, potentiostat and measurement tube to an E-chip calorimetry. Leveraging this setup, our E-chip calorimetry enables three complementary measurement modes: temperature-dependent scans to probe thermal transitions, frequency-dependent measurements to determine fragility index and isothermal measurements to monitor ion motion. Using this setup, we investigated the structural evolution of PEDOT:PSS and homogeneous OMIECs in their dry, swollen, and electrochemically doped states. In addition, we designed a special device architecture to enable operando calorimetric measurements. We observed non-uniform ion distribution within heterogeneous structures during swelling and (de)doping, leading to unique evolution patterns of segment motion and fragility in amorphous fractions. During swelling, the Tg of the PSS-rich phase is significantly reduced and approaches room temperature, while the Tg of the PEDOT-rich amorphous phase remains relatively high values. Fragility measurements indicate that swelling does not substantially alter chain rigidity of PEDOT segments, indicating a planar chain conformational in glassy phase. This enables efficient ion uptake within PSS-rich phases while preserving the hierarchical ordered structure in PEDOT-rich phases. In contrast, during dedoping, the Tg of the PSS-rich phase shows minimal change, while ions intercalate into the PEDOT-rich phase. This causes substantial fluctuations in the segmental dynamics of the PEDOT-rich amorphous phase and disrupts its chain conformational order, thereby enhancing dedoping efficiency. Specifically, films with a lower Tg and a higher m with more fibrillar morphology and loose structure, show more pronounced synergistic effect between segmental dynamics and fragility during operation. These characteristics promote both segmental motion-mediated transport in the PSS-rich phase and free-volume-mediated ion hopping in the PEDOT-rich phase, while supporting hierarchical charge carrier transport, providing the key physical descriptions for guiding the high-performance sample design. These findings elucidate the role of amorphous phase in OMIECs and underscore the potential of operando chip calorimetry in uncovering structure-property relationships in electroactive polymers.