<p>Islands provide powerful systems for studying morphological evolution, and although body size evolution in insular mammals is well documented, less is known about how integrated cranio-mandibular traits respond to the combined effects of environmental variation and geographic isolation. Here, we examine cranial and mandibular variation in house mice (<i>Mus musculus domesticus</i>) from the Canary Islands, a system characterised by repeated colonisation events and marked ecological heterogeneity. Using geometric morphometrics, we assess cranio-mandibular shape across the archipelago within an integrated morphological framework. Cranio-mandibular integration is evaluated using partial least squares, while the relative contributions of environmental and geographic factors are quantified using variation partitioning analyses. Body size varied significantly among islands but showed no clear geographic pattern. In contrast, cranial and mandibular shape exhibited strong population differentiation largely independent of size, with pronounced geographic structuring. Despite a strong signal of integration, localised shape changes were also evident, most notably affecting the coronoid process. Variation partitioning analyses revealed that both geographic structure and environmental heterogeneity contributed significantly to cranial and mandibular shape variation, although geographic factors consistently accounted for a larger proportion of morphological differentiation. These findings indicate that cranio-mandibular evolution in insular mice reflects responses to environmental variation and geographic structure, with morphological integration modulating these effects, and suggest a potential role for localised functional adaptation, phenotypic plasticity, and colonisation history. Overall, our results highlight the importance of jointly considering spatial and environmental drivers within an integrated framework to understand morphological evolution in island systems.</p>