The aim of this paper is to provide an in-depth exploration of the opportunities and challenges towards the uptake of sustainability practices (SPs) among manufacturing firms in Uganda. SPs are among the notable solutions in overcoming the challenges facing the global environment, society as well as prosperity for all. The paper utilized a qualitative research design following a review approach of relevant scientific, technical as well as government policy papers. From the review, enforcement of the available environmental laws and policies, customer’s awareness, technological innovation, organisational culture and strict governance, emerge as key drivers towards the uptake of SPs in this country. However, weak legislations and enforcement in some instances, lack of sufficient resources to invest in new technologies, high costs of financing, organisational culture, and limited awareness emerge as the main challenges facing the uptake of SPs. Furthermore, our study provides policy implications that could mitigate the challenges identified especially in a least developed country, Uganda.