Livestock production system, particularly in pastoral areas, is mainly constrained by rampant livestock diseases and seasonal feed and water shortages. In areas like Dassenech, bordering Kenya and South Sudan, this risks are pronounced due to the unavailability of appropriate prevention and control. The research was conducted with the objectives of identifying major rampant diseases and designing appropriate prevention and control strategies. A cross-sectional study was employed, conducted using both participatory epidemiology and conventional veterinary investigation. Spatial and temporal occurrence of diseases was assessed. The major five diseases in bovine were contagious bovine pleuro pneumonia (CBPP), septicemic pasteurellosis, anthrax, foot and mouth disease (FMD), and black leg, in that order of importance. Similarly, in ovine, "unknown recent disease," pneumonic pasteurellosis, brucellosis, peste des petits ruminants (PPR), and septicemic pasteurellosis were ranked, starting from the most important whereas in caprine PPR, contagious caprine pleuro pneumonia (CCPP), goat pox, brucellosis, and pneumonic pasteurellosis were ranked in that order of importance. The seroprevalence in bovine were found to be 97, 10, 18, and 15% for septicemic pasteurelosis, CBPP, FMD, and brucellosis, respectively. The seroprevalence of septicemic pasteurelosis, PPR, and brucellosis was 86, 49, and 3%, respectively, in ovine. The seroprevalence of caprine sera for CCPP, PPR, and brucellosis were 87, 42, and 0%, respectively. The prevention and control regimen, vaccination against CBPP, should be at the beginning of wet season, whereas, for FMD, it should be at the end of wet season in bovine. Brucellosis for bovine, if has to be applied, should be at the beginning of dry season. PPR vaccination for ovine should be at the beginning of wet season whereas, for caprine, it should be just before start of dry season. Furthermore, the efficacy of aforementioned vaccines and its protocol should be verified in local context. In conclusion, this finding is an alarm and requires preparation and implementation of appropriate disease prevention and control strategy in collaborated approach. Further studies have to be conducted, with particular emphasis in determining the epidemiology, and prevention and control options of FMD and brucellosis.