In 2011, the South African National TB Programme launched a policy of decentralized management of drug-resistant tuberculosis (DR-TB) in order to expand the capacity of facilities to treat patients with DR-TB, minimize delays to access care and improve patient outcomes. This policy directive was implemented to varying degrees within a rapidly evolving diagnostic and treatment landscape for DR-TB, placing new demands on already-stressed health systems. The variable readiness of district-level systems to implement the policy prompted questions not only about differences in health systems resources but also front-line actors' capacity to implement change in resource-constrained facilities. Using a grounded theory approach, we analysed data from in-depth interviews and small group discussions conducted between 2016 and 2018 with managers (n = 9), co-ordinators (n = 15), doctors (n = 7) and nurses (n = 18) providing DR-TB care. Data were collected over two phases in district-level decentralized sites of three South African provinces. While health systems readiness assessments conventionally map the availability of 'hardware', i.e. resources and skills to deliver an intervention, a notable absence of systems 'hardware' meant that systems 'software', i.e. health care workers (HCWs) agency, behaviours and interactions provided the basis of locally relevant strategies for decentralized DR-TB care. 'Software readiness' was manifest in four areas of DR-TB care: re-organization of service delivery, redressal of resource shortages, creation of treatment adherence support systems and extension of care parameters for vulnerable patients. These strategies demonstrate adaptive capacity and everyday resilience among HCW to withstand the demands of policy change and innovation in stressed systems. Our work suggests that a useful extension of health systems 'readiness' assessments would include definition and evaluation of HCW 'software' and adaptive capacities in the face of systems hardware gaps.