This paper introduces unipolar high-frequency nanosecond pulse bursts, which combine the advantages of microsecond pulsed electric fields and nanosecond pulsed electric fields, for the treatment of tumors. To take full advantage of this nonthermal pulsed electric field treatment, it is necessary to study the thermal effects of the high-electric-field nanosecond pulse bursts inside tumor tissue. A multiparametric analysis is performed based on a finite-element model of skin with a melanoma tumor that is nipped using the Tweezertrodes. The electric field ranges from 1 to 10 kV/cm, the pulsewidth ranges from 50 to 500 ns, and the frequency in the pulse bursts ranges between 100 kHz and 1 MHz. The total pulselength is <inline-formula> <tex-math notation="LaTeX">100~\mu \text{s} </tex-math></inline-formula>, and the frequency of the pulse bursts is 1 Hz. The Pennes bioheat transfer equation and the Arrhenius equation are used to calculate the temperature and the thermal damage. For pulse parameters of 5 kV/cm, 500 ns, and 1 MHz, the simulated temperature of the skin tumor is only 37.48 °C after 1 s, and the thermal damage is negligible. The temperature and thermal damage to the melanoma tumor in the skin are simulated and calculated for various electric fields, pulse widths, and frequencies. The relationship between the thermal effects on the tumor and the pulse parameters is researched, and pulse parameters for a tumor without thermal damage are ascertained. Temperature measurements of melanoma tumors in nude mice in vivo show that the change in experimental temperature in the tumors is consistent with the simulated average tumor temperature.