Information technology (IT) innovations have been vital to the success of organizations seeking to improve efficiency and productivity. IT’s global diffusion has however raised serious questions about its neutral application across cultures and contexts. This paper synthesizes a sample of the literature to conceptualize the key cultural challenges in IS innovation as, differentiation, externality, compatibility, embeddeness. The study shows that the adoption decision is challenged by differentiation, and the adoption phase exhibits issues of externality. During implementation, compatibility is the key challenge of innovators and the assimilation literature revealed that embeddeness was the cultural challenge that phase. The synthesis also revealed that the comprehension phase where adoption decisions are made was lacking significant study. The paper proposes two opportunities for research and examples of research methods that can be use to investigate pre-adoption phenomena.