Silverleaf nightshade, a highly invasive perennial weed, poses a serious threat to crops and orchards in Mediterranean regions. This weed reproduces both sexually, through seeds, and asexually, via an extensive rhizome network, contributing to its persistence and spread. Managing silverleaf nightshade is particularly challenging, requiring integrated chemical and non-chemical approaches. This study evaluated the effectiveness of preemergence and postemergence herbicides and thermal control methods applied to silverleaf nightshade at three growth stages: 2 to 3 TL, 4 to 6 TL, and 7 to 10 TL (where TL represents the true-leaf stage). Seven preemergence herbicides were tested in a dose-response experiment at rates between 0.0625× and 2× of the recommended label rate on seedling emergence from three populations. Metribuzin, pyroxasulfone, pendimethalin, and sulfosulfuron suppressed seedling emergence by 80% to 90% at 28 d after treatment. Seven postemergence herbicides were tested on the same three seed populations, and on plants grown from rhizomes. Treatments were applied at three rates: the recommended label rate (1×), and two exploratory rates, 0.5× and 2×. The biomass of the weed was reduced by more than 90% at all growth stages when aminopyralid and glufosinate were applied the 1× and 2× rates. Weed biomass was further reduced by 95% when fluroxypyr and imazapic at all application rates were applied to the weed at the 2- to 3-TL growth stage. At the 4 to 6 and 7 to 10 TL growth stages, biomass reduction >90% was achieved only at the 2× rate. Propane flaming at 33.3, 50, and 100 kg ha−1 and electrocution with 18, 45, and 90 J (which correspond to the 0.5×, 1×, and 2× application rates) were tested across the three growth stages. Both thermal methods were highly effective at the 2 to 3 TL stage by reducing biomass by >95%. The results highlight the importance of early intervention, because the efficacy of both herbicide and thermal treatments declined significantly as the weeds matured. Integrating preemergence and postemergence herbicides with thermal treatment could improve the long-term management of silverleaf nightshade in Mediterranean cropping systems.