Scientific conceptual change poses a cognitive challenge in science learning, requiring cognitive conflict resolution and restructuring of entrenched semantic knowledge. Although neuroscience implicates coordinated prefrontal cognitive control and hippocampal-temporal systems to conflict resolution and semantic memory updating, direct neural evidence of their interaction during conceptual change remains limited. Using functional MRI and Granger causality (GC) analyses, we examined neural mechanisms distinguishing successful from unsuccessful conceptual change across task complexities in 48 undergraduate and graduate STEM majors who completed 39 conceptual change tasks (19 weak restructuring task, 20 radical restructuring task). Learners exhibited greater conceptual change success during weak than radical restructuring, with enhanced BOLD activation in the superior, middle, and inferior frontal gyri (SFG, MFG, IFG), hippocampus (HIP), and superior temporal gyrus (STG) during successful versus unsuccessful conceptual change. GC analysis identified a minimal network (SFG, MFG→HIP, STG→MTG, MTG→HIP) common to both conditions, whereas successful conceptual change engaged a denser prefrontal-hippocampal-temporal network, marked by additional unidirectional (MFG→SFG, MFG→IFG, IFG→HIP) and bidirectional (MFG↔STG, STG↔HIP, MTG↔HIP) connectivity. Unsuccessful conceptual change was characterized by shallow, fragmented connectivity and limited cross-regional integration. Collectively, these findings suggest that effective conceptual change arises from coordinated neural networks integrating executive control, semantic processing, and memory updating.