Neglected Tropical Diseases (NTDs) remain endemic to many regions of sub-Saharan Africa (SSA) left behind by socioeconomic progress. As such, these diseases are markers of extreme poverty and inequity that are propagated by the political, economic, social, and cultural systems that affect health and wellbeing. As countries embrace and work towards achieving the Sustainable Development Goals (SDGs), the needs of such vulnerable populations need to be addressed in local and global arenas. The research uses primary qualitative data collected from five NTD endemic counties of Kenya: interviews key informants (n = 21) involved in NTD implementation programs and focus groups (n = 5) of affected individuals. Informed by theories of political ecology of health, the research focuses on post-devolution Kenya and identifies the political, economic, social, and cultural factors that propagate NTDs and their effects on health and wellbeing. Our findings indicate that structural factors such as competing political interests, health worker strikes, inadequate budgetary allocations, economic opportunity, marginalization, illiteracy, entrenched cultural norms and practices, poor access to water, sanitation and housing, all serve to propagate NTD transmission and subsequently affect the health and wellbeing of populations. As such, we recommend that post-devolution Kenya ensures local political, economic and socio-cultural structures are equitable, sensitive and responsive to the needs of all people. We also propose poverty alleviation through capacity building and empowerment as a means of tackling NTDs for sustained economic opportunity and productivity at the local and national level., Author summary Wellbeing is currently seen as an avenue that shapes, happiness, productivity, environmental awareness, social inclusion, and justice; however, most countries presently adopting wellbeing measures are in the global north. Neglected Tropical Diseases (NTDs) significantly compromise populations’ health and well-being in the global south, causing undesirable effects on the personal, social, and economic capabilities of communities living in endemic regions. As countries work towards achieving the Sustainable Development Goals (SDGs), it is paramount that countries in the global south adopt wellbeing measures and, in doing so, capture the lived experiences of individuals experiencing inequities, particularly as these are shaped by NTDs. In sub-Saharan Africa (SSA), political and economic power manifests across different scales, determining human-environmental interaction, distribution of resources, and the transmission of infectious agents. This paper uses a political ecology of health approach to identify the political, economic, social and cultural factors that contribute to NTDs, which are among the world’s greatest global health problems. The vast majority of people bearing the burden of NTDs reside in low-income countries. Surprisingly, as the economies of the low-income countries improve to middle-income status, NTDs continue to thrive among sub-populations of low socioeconomic status because of the unequal distribution of economic gains. As a result, NTDs are found in environments characterized by poverty and income inequality, and other inequalities in access to health services, housing, safe water, and sanitation. This paper uses political ecology of health in the primarily biomedical field of NTDs to demonstrate that inequities are embedded within the broad political, socio-cultural, and economic systems that exacerbate NTD infection. The study recommends that NTD endemic countries in SSA formulate policies that enhance equity through capacity building and empowerment enhance population wellbeing.