The increasing scale and complexity of neuroimaging datasets aggregated from multiple study sites present substantial analytic challenges, as existing statistical analysis tools struggle to handle missing voxel-data, suffer from limited computational speed and inefficient memory allocation, and are restricted in the types of statistical designs they are able to model. We introduce Image-Based Meta- & Mega-Analysis (IBMMA), a novel software package implemented in R and Python that provides a unified framework for analyzing diverse neuroimaging features, efficiently handles large-scale datasets through parallel processing, offers flexible statistical modeling options, and properly manages missing voxel-data commonly encountered in multi-site studies. IBMMA produced stronger effect sizes and revealed findings in brain regions that traditional software overlooked due to missing voxel-data resulting in gaps in brain coverage. IBMMA has the potential to accelerate discoveries in neuroscience and enhance the clinical utility of neuroimaging findings.