INTRODUCTION: We used a Programme Science platform, to generate evidence to support the implementation of programmes for sex workers in Africa. Female sex workers are estimated to make up 1.6% (1.3%-1.8%) of the population of women aged 15-49 years in Zimbabwe. We highlight how programme science can be used to help distinguish between when, where and with whom programmes need to be implemented and discuss two case studies that exemplify implementing better (Case study 1 (1 June 2019-30 June 2021) Optimizing implementation of a risk differentiated microplanning intervention) and implementing differently (Case study 2 (1 October 2016-30 September 2022) Reorientating implementation of DREAMS for young women selling sex). METHODS: Zimbabwe's nationally scaled programme for sex workers was established in 2009 in partnership with sex workers to provide comprehensive services for sex workers and generate evidence for programme design, implementation and scale up. Since inception, comprehensive data have been collected from all sex workers seeking services. As the scope of service provision has expanded so has the scope of data collection and analysis. At enrolment, sex workers are assigned an alphanumeric unique identifier which links consultations within and across programme sites. We conduct descriptive analyses of the Key Population (KP) programme data to guide programme implementation and redesign, embedding programmatic qualitative enquiry as required. RESULTS: Two case studies describing different approaches to programme optimization are presented. In the first, an optimization exercise was used to strengthen programme implementation ensuring that the KP programme got back on track after SARS-COV-2. In the second, an in-depth review of research and programme data led to a re-orientation of the DREAMS programme to ensure that young women at the highest risk of HIV acquisition were enrolled and had access to DREAMS social support interventions in turn strengthening their uptake of HIV prevention. CONCLUSIONS: Optimizing and sustaining HIV care and treatment programmes requires effective delivery with sufficient scale and intensity for population impact. Our programme science approach guided the scale up of the KP programme in Zimbabwe, providing evidence to support strategy, implementation and ongoing management, and importantly helping us distinguish between when we needed to just implement, implement better or implement differently.