Although research exists on features of effective professional development surrounding Technological Pedagogical Content Knowledge (TPACK), relatively few studies have examined the relationship of context to the acquisition of TPACK. Despite this framework’s dominance in the literature, the role that contextual factors play in the development of TPACK is not well understood. This study employed a sequential mixed methods investigation of the relationship between contextual factors and TPACK in a group of teachers from the Organization of Eastern Caribbean States during an online teacher professional development program designed to enhance their skills relating to teaching and learning online. Results demonstrated that several factors, including collaboration with colleagues, level of autonomy in teaching, and access to technology, were all associated with differences in levels of TPACK among participants and related to contextual factors such as urbanicity, age of students/parent involvement, and school/school system culture.