The efficacy of a novel topical combination of fipronil 9.8% (w/v) and (S)-methoprene 8.8% (w/v) (Fiprofort® Plus) was tested against ticks and fleas in naturally infested dogs. A total of fifty dogs were allocated in the study with ticks infestation (n = 35) and fleas infestation (n = 15). On day 0, thirty-five tick and fifteen flea infested dogs received the test formulation, a combination of fipronil 9.8% (w/v) and (S)-methoprene 8.8% (w/v) spot-on solution. Ticks and flea counts were taken on days 0 (pretreatment) and 3, 7, 14, 21, 28, and 35 after treatment. Blood samples were collected for evaluation of haematological parameters on days 0 (pretreatment) and 7, 21, and 35 after treatment. All the adult ticks and fleas collected were identified as Rhipicephalus sanguineus and Ctenocephalides felis, respectively. The efficacy of spot-on formulation against ticks was 34.00% (day 3), 53.14% (day 7), 62.71% (day 14), 65.48% (day 21), 59.80% (day 28), and 58.82% (day 35), whereas against fleas it was 38.00% (day 3), 64.34% (day 7), 89.67% (day 14), 95.40% (day 21), 100.00% (day 28), and 100.00% (day 35). Haematological parameters for ticks and fleas infested dogs were statistically nonsignificant as compared to control. The combination of fipronil and (S)-methoprene eliminated the existing ticks and fleas infestation and prevented the dogs from flea and tick infestation for four weeks.