Cultural heritage is a testimony of past human activity, and, as such, cultural objects exhibit great variety in their nature, size, and complexity, from small artefacts and museum items to cultural landscapes, and from historic buildings and ancient monuments to city centers and archaeological sites. Cultural heritage around the globe suffers from wars, natural disasters, and human negligence. More specifically, cultural goods and artefacts are put at risk through several anthropogenic actions: Anthropogenic threats take various dimensions, ranging from theft from museums, private collections, and religious buildings, smuggling of and illicit trade in cultural goods, the irremediable looting and demolition of archaeological sites by clandestine excavators, or simply neglect of heritage sites. Illicit trading has expanded dramatically recently, especially in areas affected by armed conflicts and natural disasters, either aiming at destroying collective memory and dismembering people’s identity or mostly motivated by the pursuit of profit. Moreover, the illicit trafficking of cultural goods contributes to the funding of terrorism, organized crime, and money laundering. The mission of ENIGMA, a EUR 4 million EU funded project, is to achieve excellence in the protection of cultural goods and artefacts from man-made threats by contributing to their identification, traceability, and provenance research, as well as by safeguarding and monitoring endangered heritage sites. ENIGMA objectives are designed to help the involved stakeholders better respond to this complex and multi-dimensional problem and leverage active collaboration by fostering and enabling interlinking of databases, and evidence-based deployment of preventative measures.