As a result of recent advancements in design and optimization of high-pressure processing units, the technology is gaining rapid adoption across various sectors of food manufacturing, thus requiring extensive microbiological hurdle validation studies for efficacious and feasible utilization of the technology. Commercial adoption of high-pressure processing is gaining momentum of industrial importance because of recent advances in the engineering of pressure-based pasteurization units. With tremendous ability of plethora of microorganisms to move towards fitness through vertical and horizontal gene transfer mechanisms, prevention of natural and anthropogenic pathogens of public health concern is a daunting task and a moving target. Current study discusses, Reducing the Cost Associated with High Pressure Processing: Efficacious Alternatives to the Current Standard Procedure in the Food Manufacturing Industry, with microbiological challenge studies for inactivation of the pathogen exposed to various times and intensity levels of elevated hydrostatic pressure. Elevated hydrostatic pressure is a non-thermal procedure that exposes pathogens to pressures of up to 80,000 PSI (>550 MPa). Various times (3, 4, and 5 minutes) at pressure intensity levels of 600 MPa, (87K PSI), 550 MPa (79K PSI), 480 MPa (70K PSI), 415 MPa (60K PSI), and 345 MPa (50K PSI) of elevated hydrostatic pressure (Hub880 Explorer), were investigated at 4C and for 45C for inactivation of Shiga toxin-producing Escherichia coli O157:H7 (STEC) (ATCC numbers BAA 460, 43888, 43894, 35150, 43889, and 43890) respectively, Big Six non-O157 Shiga toxin-producing E. coli (nSTEC) (ATCC numbers BAA 2196, 2193, 2215, 2440, 2219, and 2192) respectively, Salmonella serovars (ATCC numbers 13076, 8387, 6962, 9270, and 14028) respectively, and Listeria monocytogenes (ATCC numbers 51772, 51779, BAA 2657, and BAA 13932). Studies were conducted in two biologically independent repetitions as a blocking factors of a randomized complete block design containing three repetitions per time/treatment within each block, analyzed statistically using GLM procedures of SAS 9.4 software at type one error level at 5% using Tukey- and Dunnett-adjusted ANOVA. A Barocycler Hub840 unit, equipped with a water jacket and circulating water bath for precise application of hydrostatic pressure and controlled temperature was utilized. Up to 0.95 and 2.60 log reductions (P<0.05) of non-habituated Shiga toxin-producing Escherichia coli Non-O157 at planktonic stages were achieved using application of pressure at 345 MPa and 550 MPa for 5 minutes and 4 minutes, respectively at 4C. Up to 4.42 and 5.10 log reductions (P<0.05) of non-habituated Shiga toxin-producing Escherichia coli Non-O157 at planktonic stages were achieved using application of pressure at 345 MPa and 480 MPa for 5 minutes and 4 minutes, respectively at 45C. Up to 1.63 and 3.14 log reductions (P < 0.05) of non-habituated Listeria monocytogenes at planktonic stages were achieved using application of pressure at 345 MPa and 600 MPa for 5 minutes and 3 minutes, respectively at 4C. Up to 4.91 and 6.37 log reductions (P < 0.05) of non-habituated Listeria monocytogenes at planktonic stages were achieved using application of pressure at 550 MPa and 480 MPa for 4 minutes, respectively at 45C. Up to 2.87 and 5.82 log reductions (P< 0.05) of non-habituated Salmonella serovars at planktonic stages were achieved using application of pressure at 345 MPa and 550 MPa for 5 minutes and 4 minutes, respectively at 4C. Up to 5.17 and 6.79 log reductions (P< 0.05) of non-habituated Salmonella serovars at planktonic stages were achieved using application of pressure at 415 MPa and 600 MPa for 5 minutes and 3 minutes, respectively at 45C. Up to 0.86 and 1.35 log reductions (P<0.05) of non-habituated Shiga toxin-producing Escherichia coli O157:H7 at planktonic stages were achieved using application of pressure at 345 MPa and 480 MPa for 5 minutes and 4 minutes, respectively at 4C. Up to 2.02 and 6.12 log reductions (P<0.05) of non-habituated Shiga toxin-producing Escherichia coli O157:H7 at planktonic stages were achieved using application of pressure at 345 MPa and 550 MPa for 5 minutes and 4 minutes, respectively at 45C. Results of this study could be incorporated as a part of predictive public health microbiology modeling and risk assessment analysis for prevention of pathogen related disease and illness episodes.