The current study aimed to investigate mathematical modeling, drying kinetics, and thermodynamic properties for cost-effectively drying marjoram leaves under different operating pressures (OPs) and drying temperatures (DTs). Three DTs of 40, 50, and 60◦C and three OPs of (atm) atmospheric, −5 kPa, and −10 kPa were used in this study. All drying processes were conducted using the developed vacuum dryer (DVD) and a constant layer thickness of 1 cm and initial moisture content of 817.43 on a dry basis (d.b.). The results obtained showed that increasing the DT from 40 to 60◦C at OPs of atm, −5 kPa, and −10 kPa led to a decrease in the drying time by about 55.6%, 36.4%, and 42.9%, respectively. On the other hand, decreasing the OP from atm to −10 kPa resulted in a decrease in drying time of about 58.8%, 45.5%, and 50% at DTs of 40, 50, and 60◦C, respectively. The moisture diffusivity (Deff) ranged between 1.13 and 5.51 × 10−9 m2/s, with the highest value of Deff observed at an OP of −10 kPa and a DT of 60◦C. Under these conditions, the activation energy (AE) was minimal, at approximately 2.68 kJ/mol. Mathematical modeling revealed that the Modified Midilli (I) model was the most suitable for describing the drying kinetics of marjoram leaves under experimental conditions. Among the thermodynamic parameters of marjoram leaves, it was observed that enthalpy values decrease with increasing DT and decreasing OP. Additionally, all tests showed negative entropy, suggesting that the chemical adsorption and/or structural modifications of the adsorbent are responsible for these results. The economic analysis revealed that drying marjoram leaves at an OP of -10 kPa and a DT of 60◦C resulted in yearly cost savings of up to USD 2054.19 and reduced the investment payback period to approximately 0.139 years (about 2 months).