Cannabis (Cannabis sativa L.) is a dioecious plant cultivated worldwide for thousands of years. Besides the narcotic and therapeutic effects, Cannabis can be used as raw materials in multiple fields, including bioenergy, textiles, food, and ecological restoration. It is also an efficient bioremediation agent for contaminated soil, as well as greenhouse gas absorption. With the expansion of the market, there has been an increased demand to develop Cannabis cultivars with enhanced traits. As a major science breakthrough, the advent of the CRISPR/Cas system will revolutionize the basic and applied research in Cannabis. This article provides an overview of the recent advances in the optimization of a transformation system and in the gene editing of Cannabis. To achieve the full potential of this environmentally friendly and sustainable crop, we highlight future directions of genetic modification as well as several bottlenecks to overcome.