This paper presents a framework for the development of socio-ecological systems towards enhanced sustainability. Emphasis is given to the dynamic properties of complex, adaptive social-ecological systems, their structure and to the fundamental role of agriculture. The tangible components that meet the needs of specific projects executed in Kenya and Ethiopia encompass project objectives, innovation, facilitation, continuous recording and analyses of monitoring data, that allow adaptive management and system navigation.Two case studies deal with system navigation through the mitigation of key constraints; they aim to improve human health thanks to anopheline malaria vectors control in Nyabondo (Kenya), and to improve cattle health through tsetse control and antitrypanosomal drug administration to cattle in Luke (Ethiopia). The second case deals with a socio-ecological navigation system to enhance sustainability, establishing a periurban diversified enterprise in Addis Ababa (Ethiopia) and developing a rural sustainable social-ecological system in Luke (Ethiopia).The project procedures are briefly described here and their outcomes are analysed in relation to the stated objectives. The methodology for human and cattle disease vector control were easier to implement than the navigation of social-ecological systems towards sustainability enhancement. The achievements considerably differed between key constraints removal and sustainability enhancement projects. Some recommendations are made to rationalise human and cattle health improvement efforts and to smoothen the road towards enhanced sustainability: i) technology system implementation should be carried out through an innovation system; ii) transparent monitoring information should be continuously acquired and evaluated for assessing the state of the system in relation to stated objectives for (a) improving the insight into the systems behaviour and (b) rationalizing decision support; iii) the different views of all stakeholders should be reconciled in a pragmatic approach to social-ecological system management.Significance for public healthRecently, there is a growing interest in studying the link between human, animal and environmental health. The connection between these different dimensions is particularly important for developing countries in which people face the challenge of escaping vicious cycle of high diseases prevalence, food insecurity driven by absolute poverty and population growth, and natural capital as a poverty trap. The design and implementation of such efforts, aiming at human health improvement and poverty alleviation, should be framed into adaptive social-ecological system management perspectives. In this paper, we present few case studies dealing with human health improvement through anopheline malaria vectors control in Kenya, cattle health improvement through tsetse vectored nagana control, antitrypanosomal drug administration to cattle in Ethiopia and with the development of rural sustainable communities in Ethiopia. Some recommendations...