The alignment between information systems strategy and business strategy as an important driver of competitiveness has predominantly been assessed through quantitative methods without exploring in detail factors that influence strategic alignment and their implications for perceived business performance. Most IS-business strategic alignment studies dominantly focus on entire business and IS strategies resulting in many findings that are too general and inconclusive. This study aims at assessing strategic alignment factors, their interrelationships, and how they influence the IS-business alignment and its consequential effect on the performance of six universal banks in Ghana. The study followed the systematic procedure of grounded theory design and adopted qualitative dominant crossover mixed analysis. The findings of the study indicate strategic alignment between information systems strategy and technological innovation impacts positively on the performance of a firm where IT utilization complements resources and capabilities.