Parental drinking problem can directly effect on their children. For this reason, children of alcoholics (COAs) tend to show negative outcomes while they are growing up, such as depression, anxiety, suicidal ideation, substance abuse or interpersonal difficulties. However, there are several factors that effect on COAs that minimize or maximize the impact of adverse experiences related to their parental drinking problem, and it is important to understand those factors to prevent or minimize the negative outcomes in COAs. Thus, this study examined both risk and protective factors of COAs, which affect their adverse outcomes. A systematic review was conducted by following PRISMA statement. Three databases—PubMed, CINAHL, and PsycINFO—were searched, and total 39 articles were found and discussed. This study identified risk, protective, and biological factors in COAs, and categorized into four levels: individual, parental, familial and social. Each level contains specific factors that positively or negatively affect the development in COAs. In addition, biological differences between COAs and non-COAs and between resilient COAs and vulnerable COAs were discussed. Findings from this study should be applied to COAs and adult COAs through evidence-based interventions in order to help them in terms of preventing or minimizing the negative outcomes they might experience in their lives.