With the advent of innovative technologies and multi-dimensional researches along the setting of entrepreneurship development, philosophy, context and business handling has been transformed from being traditional to innovative. Depending on diversity and nature of the transformation, innovation has been shifted from closed to open to crowdsourcing innovation. Ranging from small entrepreneurs to corporate business houses are being immensely benefited by the innovation techniques, especially utilizing information and communication technologies. However, the road to innovation, despite being a paradigm shift is not smooth and ready for many, particularly the small and medium enterprises who mainly deal with the clients at the outer peripheries of the social circle. This chapter synthesizes issues of opportunities and challenges for small and medium enterprises by carrying out a broad literature review and synthesis. Furthermore, the chapter will provide a few research hints to be applicable for researchers and research institutions.