Automated spraying practices are inevitable for modern polyhouse management to attain a broader objective of minimizing human exposure to agrochemicals. In the present study, an automated mobile robotic sprayer (AMRS) was developed to combat the increased human intervention and safeguard agricultural workers from potential health hazards. The system mainly comprises embedded sensors (ultrasonic, proximity, XBee) and controllers (Arduino, PLC). The controller drives the system on a piping track between the rows as well as on the head space achieving end-to-end automation for spraying operations. The system performance was evaluated on the tomato crop with respect to the physiological traits, yield and economics. Additionally, the study leveraged response surface methodology to optimize forward speed, spray distance, and working pressure of AMRS on the responses, droplet density, coverage, volume mean diameter (VMD) and application rate. Optimization of forward speed (0.79 km/h), spray distance (250 mm) and working pressure (0.40 MPa) resulted in 90.7 droplets/cm 2 droplet density, 47.1% coverage, 170.2 μm VMD and 86.0 mL/m 2 of application rate. Ergonomic aspects of AMRS were assessed by the parameters, human exposure, discomfort and postural assessment with respect to knapsack sprayer. The working heart rate of 103 beats/ min, work pulse of 12 beats/min, oxygen consumption rate of 916 mL/min and energy expenditure rate of 18.7 kJ/min recorded during the ergonomic evaluation of the AMRS were 25%, 75%, 42%, and 41% lower compared to manual spraying, respectively. Moreover, three-six times higher work pulse, cardiac cost, body part discomfort score and overall discomfort rating were observed which indicated more drudgery involved in manual spraying. State-of-the-art system developed for polyhouses would minimize the drudgery and health hazards, significantly. The system's resilience and effectiveness pave the way for its wider deployment where the use of agrochemicals are prevalent, particularly in small-size polyhouses.