This paper presents the main messages of a South American expert roundtable (ERT) on the unintended side effects (unseens) of digital transformation. The input of the ERT comprised 39 propositions from 20 experts representing 11 different perspectives. The two-day ERT discussed the main drivers and challenges as well as vulnerabilities or unseens and provided suggestions for: (i) the mechanisms underlying major unseens; (ii) understanding possible ways in which rebound effects of digital transformation may become the subject of overarching research in three main categories of impact: development factors, society, and individuals; and (iii) a set of potential action domains for transdisciplinary follow-up processes, including a case study in Brazil. A content analysis of the propositions and related mechanisms provided insights in the genesis of unseens by identifying 15 interrelated causal mechanisms related to critical issues/concerns. Additionally, a cluster analysis (CLA) was applied to structure the challenges and critical developments in South America. The discussion elaborated the genesis, dynamics, and impacts of (groups of) unseens such as the digital divide (that affects most countries that are not included in the development of digital business, management, production, etc. tools) or the challenge of restructuring small- and medium-sized enterprises (whose service is digitally substituted by digital devices). We identify specific issues and effects (for most South American countries) such as lack of governmental structure, challenging geographical structures (e.g., inclusion in high-performance transmission power), or the digital readiness of (wide parts) of society. One scientific contribution of the paper is related to the presented methodology that provides insights into the phenomena, the causal chains underlying “wanted/positive” and “unwanted/negative” effects, and the processes and mechanisms of societal changes caused by digitalization.