Plant bacterial wilt is caused by Ralstonia solanacearum, a soilborne pathogen that infects plant conduits, leading to wilt disease. It is extremely difficult to cure plants infected with Ralstonia solanacearum; however, bactericide-loaded beads with hot-/wet-responsive properties may be able to release a biocide in line with the increase in the hot-/wet-associated activity of Ralstonia solanacearum, effectively killing the pathogenic cells and providing high levels of plant protection. A biopesticide, Tetramycin, was embedded in corn kernel powder (CKP)-based cores. An oil-phase mixture was sprayed onto the core surface to form a hot-/wet-responsive intermediate shell (IMS). Subsequently, a layer of ethyl cellulose (EC) and hydroxypropyl methyl cellulose (HPMC) was coated onto the IMS to create a single wet-responsive outer shell (OTS). The ratios of the components in the cores, including the corn kernel powder (CKP), xanthan gum (XG), and Tetramycin, were optimized, as well as those of the IMS, including pentaerythrityl tetrastearate (PETS), pentaerythrityl tetraoleate (PETO), polyethylene glycol stearate (PEG400MS), and polyethylene glycol monooleate (PEG400MO), and those of the outer shell (OTS), including ethyl cellulose (EC) and hydroxypropyl methyl cellulose (HPMC). A texture performance analysis, differential scanning calorimetry (DSC) analysis, thermogravimetric analysis (TGA), temperature and humidity response performance tests, scanning electron microscope (SEM) observations, and a field effectiveness test were conducted to characterize the Tetramycin-loaded beads. The results indicated that the optimal formula for the bead cores comprised a mass ratio of CKP/Tetramycin solution/XG = 13.5:23:2. The preferred mass ratio for IMS was PETS/PETO/PEG400MO = 10:30:10, and the formula for the applicable OTS consisted of a mass ratio of EC/HPMC = 5:1. In soil with a temperature of 30–35 °C and humidity of 30%, the release period of the Tetramycin-loaded beads, with a cumulative release rate of over 95%, could last up to 35 days. Furthermore, the Tetramycin-loaded beads exhibited a gradual and multi-cyclic release process under alternating hot/wet and dry/cold environments. The relative preventive efficacy of 54.74% on tobacco was revealed at a field-testing scale. A significant reduction in the abundance of Ralstonia solanacearum was also observed under treatment with the Tetramycin-loaded beads. The early fungal community structure exhibited higher consistency compared to the control. However, in the later stage, the diversity differences between the soil layers were restored. In conclusion, Tetramycin-loaded beads that could effectively respond to temperature and humidity fluctuations were developed, resulting in enhanced disease prevention efficacy and offering broad prospects for the prevention and control of Ralstonia solanacearum in agricultural settings.