Background The increasing reports of resistance to pyrethroid insecticides associated with reduced efficacy of pyrethroid-only interventions highlight the urgency of introducing new non-pyrethroid-only control tools. Here, we investigated the performance of PBO-pyrethroid (PermaNet 3.0 (P3.0)) and dual active ingredients (AI) nets (Interceptor G2 (IG2) containing pyrethroids and chlorfenapyr) and Royal Guard (RG)- containing pyrethoids and pyripoxyfen) against pyrethroid-resistant malaria vectors in Cameroon.Methods The efficacy of these tools was first evaluated on Anopheles gambiae and Anopheles funestus s.s using cone/tunnel assays in five sites across the country. In addition, experimental hut trials (EHT) were performed to evaluate the performance of these nets in semi-field conditions where An funestus predominate using unwashed and 20 times washed nets. Furthermore, pyrethroid-resistant markers were genotyped in dead vs alive, blood-fed vs unfed mosquitoes after exposure to these nets to evaluate the impact of known pyrethroid resistance markers on performance of the new nets.Results IG2 was the most effective net against wild pyrethroid -resistant An funestus followed by PermaNet 3.0. In EHT, this net induced up to 87.8% (95% CI 83– 92%) mortality and 55.6% (95% CI 48– 63%) after 20 washes whilst unwashed pyrethroid-only net (Royal sentry) killed just 18% (95% CI 13–23%) of host-seeking An. funestus. The unwashed P3.0 killed up to 54% (95% CI 44–63%) of field-resistant mosquitoes and 47% (95% CI 38– 57%) when washed 20 times. IG2 and P3.0 also provided better personal protection (blood feeding inhibition 66.2% and 92.8%) compared to pyrethroid-only net RS (8.4%) RG (77.84%). Interestingly, a negative association was found between kdrW and the chlorfenapyr-based net IG2 (χ2 = 138; P < 0.0001) with RR mosquitoes predominantly found in the deadConclusions The high mortality recorded by Interceptor G2 against pyrethroid-resistant An. funestus in this study provides first field evidence of high efficacy against this major malaria vector in Cameroon. However the efficacy of this tools should be assessed in other locations and on other major malaria vectors across the country.