Advances in spatially-resolved transcriptomics (SRT) technologies have propelled the development of new computational analysis methods to unlock biological insights. The lowering cost of SRT data generation presents an unprecedented opportunity to create large-scale spatial atlases and enable population-level investigation, integrating SRT data across multiple tissues, individuals, species, or phenotypes. Here, unique challenges are described in the SRT data integration, where the analytic impact of varying spatial and biological resolutions is characterized and explored. A succinct review of spatially-aware integration methods and computational strategies is provided. Exciting opportunities to advance computational algorithms amenable to atlas-scale datasets along with standardized preprocessing methods, leading to improved sensitivity and reproducibility in the future are further highlighted.