<b><i>Background:</i></b> Pancreatic cancer (PC) is one of the deadliest cancers worldwide for which little clinical progress has been made in the last decades. Furthermore, increased trends of PC mortality rates have been reported in Westernised countries. PC is usually diagnosed in advanced stages, precluding patients of an effective treatment. Identifying high-risk populations and early detection markers is the first and crucial step to impact on these figures and change the PC horizon. <b><i>Aims/Objectives:</i></b> To discuss the published body of evidence on host and tumor genomics promising markers for primary and/or secondary personalised PC prevention, as well as the future perspectives in the field. <b><i>Methods:</i></b> A review of the literature was performed to identify germline and tumor DNA and RNA markers that showed potential usefulness in defining the high-risk population, diagnosing the disease early, and identifying new carcinogens associated with PC. <b><i>Results:</i></b> Only high-penetrance inherited mutations are used, at present, to define the high-risk PC population. Although there are some promising genomics markers to be used as early detection tests, none has been validated adequately to be integrated into the clinics routine. <b><i>Conclusions:</i></b> Despite of important efforts made in the recent time, little progress has been made to better characterise high-risk PC populations and to identify genomics-based markers for its early diagnosis. PC rates continue to rise, and this disease is becoming a real public health problem in the Westernised world. International and multidisciplinary strategies to identify new markers and properly validate the promising ones are urgently needed to implement cost-efficient primary and secondary prevention interventions in PC.