It is a common practice in the dairy industry to nanofilter (NF) milk protein concentrate (MPC) to increase the solids content before drying to improve drying efficiency. Previous research has demonstrated that temperature and hydrodynamic cavitation (HC) have a significant impact on the viscosity of MPC. A reduction in viscosity could potentially increase the level of concentration that can be achieved with nanofiltration. The objective of this study was to evaluate the impact of temperature and hydrodynamic cavitation on the efficiency of nanofiltration and microbial quality of MPC. Three replicates of MPC80 (20.07, 20.61 and 20.05% total solids) were concentrated using nanofiltration membrane (Parker ATF 7938-LS02-ST, spacer 65 mil, surface area 22.5 m² with a 200 Da molecular weight cut off). Four different NF treatments were utilized including: NF at 22°C (NF22); NF at 50°C (NF50); HC before NF at 22°C (HCNF22); and HC before NF at 50°C (HCNF50). The HC was performed with a rotor speed of 50 Hz and flow rate 100 L/h and was applied just before NF. All treatments were nanofiltered until the permeate flux dropped to less than 0.1 LMH. The average flux of nanofiltration was 1.53, 3.20, 1.59, and 3.10 LMH and the final TS of retentate was 25.7, 29.7, 27.4, and 31.9% respectively for the NF22, NF50, HCNF22, and HCNF50 treatments. The average flux and final total solids was significantly (P < 0.05) higher for NF conducted at 50°C as compared with 22°C. HC did not have a significant (P > 0.05) impact on average flux but did significantly increase (P < 0.05) the final TS at 22 and 50°C. The final viscosity of the NF retentate corresponded to the final TS reached and was 67, 269, 77 and 453 cP for the NF22, NF50, HCNF22, and HCNF50 treatments, respectively. The standard plate count (SPC) of the retentate before drying was 3.9 × 10⁴, 1.10 × 10⁵, 7.6 × 10⁴ and 7.3 × 10⁵ for the NF22, NF50, HCNF22, and HCNF50 treatments, respectively. This study determined that increasing the NF temperature improves nanofiltration performance and the level of total solids achieved but also increased the SPC count of the final retentate.