IT strategic alignment remains a key concern for business executives over decades. Unfortunately, prior empirical studies tend to ignore the relevance of cultural and capability dimensions to IT strategic alignment. Consequently, whether IT-related orientation and capabilities are adequate for attaining organizational goals and leading to business values still requires exploration. This study adopts three perspectives to understand why and how IT strategic alignment can be achieved through IT-related orientation and capabilities in program (i.e. project portfolio), management, and flexibility. This study develops a model to examine the relationships among such IT-related orientation, IT capabilities, IT strategic alignment, and subsequent business performance. Accordingly, seven hypotheses were proposed and the model was tested with Partial Least Square technique based on the data collected from a survey of 209 manufacturing firms in Taiwan. The results support our model with seven hypotheses confirmed. By focusing on relevant IT-related orientation, IT capabilities, and IT strategic alignment, this study extends the literatures on program (project portfolio) management, IT capability, and strategic management by manifesting the effects the studied constructs from the bridging, transformative, and adaptive perspectives. Implications of the results are provided and limitations and future research directions are discussed.