Housefly, Musca domestica L. is a cosmopolitan insect pest responsible for causing nuisance, food spoilage and act as a vector of many pathogenic diseases in man and animals. Insecticide resistance in M. domestica is becoming a major concern therefore alternative control measures are getting importance. Entomopathogenic fungi provide the potential for the management of M. domestica due to its natural prevalence in M. domestica populations. Keeping in view the importance of this pest and potentials of entomopathogenic fungi for its management following experiments were conducted. The virulence of different local isolates of Beauveria bassiana (Balsamo) Vuillemin, Metarhizium anisopliae var. anisopliae (Metschnikof) Sorokin and Isaria fumosorosea (Wize) Brown and Smith on M. domestica was evaluated by two bioassay techniques i.e., immersion and bait method for both larvae and adults. Data evidently showed a broad range of concentration dependent response on both stages (larvae and adults).In addition, due to the lower LC50 values and shorter lethal time B. bassiana (Bb-01), M. anisopliae var. anisopliae (Ma-4.1) and I. fumosorosea (If-03) proved to be the most virulent isolates against the housefly larvae and adults. In addition, fungal infections reduced the survival of housefly regardless of their sex and decreased the egg production in females. The effect of concentration and exposure time of entomopathogenic fungi, B. bassiana (Bb-01, Bb-08), M. anisopliae var. anisopliae (Ma-2.3, Ma-4.1) and I. fumosorosea (If-03) isolates were evaluated for M. domestica survival. B. bassiana, M. anisopliae var. anisopliae and I. fumosorosea have shown to infect and reduce the survival of M. domestica with a concentration dependent response for all the tested fungal isolates. Moreover, longer exposure to higher concentrations resulted in maximum reduction in M. domestica survival. B. bassiana (Bb 01) and M. anisopliae var. anisopliae (Ma-4.1) isolates proved to be more pathogenic to M. domestica than other isolates. The effect of B. bassiana, M. anisopliae var. anisopliae and I. fumosorosea in combination with some synthetic insecticides (acetamiprid, bifenthrin, emamectin benzoate, fipronil, imidacloprid and lufenuron) against M. domestica was assessed using a bait method. Flies showed concentration dependent response and insecticides i.e. acetamiprid, emamectin benzoate, imidacloprid and lufenuron showed higher mortality in combination with insect pathogenic fungi than expected with significantly synergistic interactions. Application of fungi and insecticides mixtures showed a noteworthy reduction in adult longevity, fecundity, egg hatching, percent pupation and pupal weight, while larval and pupal durations were prolonged (P<0.05). In addition, the combined effects of B. bassiana, M. anisopliae var. anisopliae and I. fumosorosea with insecticides (chlorpyriphos, deltamethrin, endosulfan and profenophos) were evaluated against M. domestica using the bait method. M. domestica showed a wide range and concentration dependent response towards combined treatments of fungi and insecticides i.e. deltamethrin and endosulfan showed higher mortality in combination with entomopathogenic fungi than expected with significant synergistic interactions. Further, the combined effects of fungi and insecticide mixtures showed a significant effect on the biological parameters including longevity, fecundity, percent hatching, larval duration, percent pupation, pupal weight and duration of M. domestica and its progeny, except for adult emergence and sex ratio. Supplementing, effectiveness of nine different insecticides (acetamiprid, bifenthrin, chlorpyriphos, deltamethrin, emamectin benzoate, fipronil, imidacloprid, lufenuron and profenophos) were evaluated for their impacts on biological and biochemical parameters of M. domestica with the aid of bait method. Adult M. domestica showed a wide-ranging and concentration dependent response towards insecticides. Calculated LC10, LC30 and LC50 of insecticides showed impact on biological aspects i.e., longevity, fecundity, hatching percentage, pupation percentage pupal weight, pupal period, adult emergence and sex ratio of M. domestica. In addition, enzyme activity at LC10, LC30 and LC50 of insecticides showed elevated levels of total glutathione S-transferases (GST), total esterases (EST), acetylcholinesterase (AChE), acid and alkaline phosphates activities. Moreover, impact of B. bassiana, M. anisopliae var. anisopliae and I. fumosorosea isolates on life history traits and detoxification enzymes activities of M. domestica were evaluated. Baits were incorporated with LC10, LC30 and LC50 concentrations as treatment levels and concentration dependent response was observed with significant reduction in adult longevity, fecundity, pupal weight and pupal duration (P<0.05). However, hatching percentage, larval duration, pupal percentage, adult emergence and sex ratio were non-significantly different after fungal application in the progeny. Fungal application resulted in elevated levels of total GST, total EST, acid and alkaline phosphatases. In addition, suppressed activity of AChE was observed after fungal treatment at 0.05% significance level. The combination of B. bassiana and imidacloprid was investigated against a susceptible and a resistant M. domestica population. Fungus and insecticide were tested alone and in combinations at LC30. Significant synergistic interactions between B. bassiana and imidacloprid were observed with increased mortality rates of the combined treatment as compared to individual treatment in housefly strains 772a (susceptible) and 766b (resistant). Significant differences in the GST and P450 activities for both strains were found. Female 766b flies caused 15- to 237-fold increases in gene expression of xenobiotics for B. bassiana and 23- to 120-fold changes for imidacloprid. B. bassiana, M. anisopliae var. anisopliae and I. fumosorosea derived toxic crude proteins were evaluated against M. domestica survival. A significant effect was observed on the survival of M. domestica with isolates Bb-01, Ma-4.1, and If-03 which showed maximum percent mortalities exhibiting a concentration and exposure time based response. The crude protein concentrations i.e., 8 and 10 mg/mL caused the maximum mortality (100.0%) of M. domestica population in 2.1 to 3.8 days. In addition, the lowest exposure of duration (96 hrs) of houseflies to B. bassiana (Bb-01) crude protein (10 mg/mL) caused 100.0% mortality of tested population as compared to other isolates.