Digital transformation has reshaped contemporary society, affecting fundamental human aspects, such as workplaces, learning environments, and quality of life. In this context, Digital Skills have emerged as indispensable. However, their connection to Well-being has not been sufficiently studied. To address this gap, we conducted a systematic literature review to explore the conceptualization and operationalization of these two constructs. Our findings revealed a predominantly positive association between Digital Skills and both hedonic and eudaimonic Well-being, along with a mitigating effect on certain concepts negatively associated with Well-being such as Stress and Anxiety. Interestingly, some studies have presented contrasting results, highlighting the influence of participants’ characteristics and contextual factors.