The viability of an energy-sustainable greenhouse in Lesotho and notable, solar photovoltaic thermal (PVT) assisted greenhouse heating, cooling and dehumidification in weather conditions in Lesotho is established. Results for solar PVT assisted temperature regulation incorporating thermal load assessment, dehumidification modelling, and whole system simulation are presented for two representative locations analysed: Leribe in the lowlands, noted for being the agricultural site in Lesotho, and Mokhotlong in the highlands, typified by cooler weather and prolonged heating needs. The proposed solar PVT-assisted approach supported solar fractions of 87.6% in Leribe and 80.6% in Mokhotlong; energy savings of 6,764–6,936 kWh/year and CO₂ reductions of 1,740–1,944 kg/year; Net Present Values above US$ 53,000, Savings-to-Investment Ratios exceeding 3.0, and a discounted payback period of five years. The study results are encouraging and the next step is to set up a trial on a significant scale to further confirm the merits of solar PVT-assisted greenhouse microclimate control.