During the last decade, Pinus strobus L. trees in the Appalachian Mountain region of the United States have been displaying symptoms of dieback, including branch flagging, resinosis, and crown thinning. Many of these economically and ecologically important trees also have a scale insect, Matsucoccus macrocicatrices Richards, and various fungal pathogens associated with canker formation. For this study, we evaluated the health of P. strobus in 40 sites across the southern Appalachian Mountains, modeled the relationships between P. strobus health and abiotic and biotic conditions, and assessed correlations among P. strobus saplings, M. macrocicatrices, and cankers. Overall, we found that M. macrocicatrices and a canker-forming fungus, Caliciopsis pinea Peck, were present in 85% and 87.5% of the 40 sites, respectively. Pinus strobus health rating was associated with DBH, tree density, and latitude, where larger diameter P. strobus trees in less dense stands were healthier than smaller diameter trees in denser stands, and trees in Virginia were less healthy than trees in Georgia. Positive correlations were present within the tripartite, P. strobus-M. macrocicatrices-canker complex, suggesting that sapling dieback is associated with M. macrocicatrices and cankers. Further exploration of the relationships among M. macrocicatrices, cankers, and site conditions are encouraged to better understand the ecological drivers behind the P. strobus dieback that is occurring in the Appalachian Mountains.