Background: Problematic khat use, not khat use per se, is a public health and social concern for the public, researchers, and policy makers. However, the construct problematic khat use is not well-established and not fully recognized in the modern definition of substance use disorders including Diagnostic Statistic Manual (DSM-5) and international classification of diseases (ICD-10), although DSM-5 included it in the “stimulant use disorder” category. Existing scoping reviews have focused on khat use, which could not allow the differentiation of khat use from problematic khat use. Thus, the aim of this systematic review was to define and validate the construct problematic khat use. Methods: This systematic review was reported following the PRISMA guidelines. We searched all English language studies without publication date restriction from 5 databases; PubMed, EMBASE, psychINFO, SocINDEX, and Google scholar. All studies that defined, explored, evaluated, or measured the construct problematic khat use were included. Adapted data extraction tool and criteria for quality evaluation were employed. We presented the results in tables and thematic synthesis of the major findings. Result: Overall, 30 qualitative and cross-sectional design studies were included. Associated harms with khat use, an increased amount used, increased frequency of use, and withdrawal experiences were indicators of problematic khat use. Using khat on an average of 3 or more times per week and using other psychoactive substances during and after khat use were frequently used to define problematic khat use. The most frequently reported withdrawal symptoms were depressed mood, irritability, fatigue, lack of motivation, increased sleep, and appetite. The existing measures (severity of dependence scale and DSM-5) of problematic khat use had psychometrically acceptable properties in terms of construct, criterion, and convergent validity, but they are poor in terms of other domains of validity including content, conceptual, and semantic validity. Conclusion: Problematic khat use constitutes, but is not limited to, harms, increased use over time, and frequent engagement in other psychoactive substances misuse. Khat use is different from problematic khat use since it is occasional and used for prayer, social, and functional reasons. Strong empirical studies that could establish thresholds for patterns of problematic khat use and a culturally suitable problematic khat use measures that follows a bottom-up approach of scale development are warranted.