Super drug resistance (PDR/EDR) in microbial strains has been a continuous phenomenon in nosocomial and miscellaneous infections. The load of these bugs has inflated over worldwide. Microbes evolve such phenomena involving mutational processes, hyper performance of pumping out systems, synthesis of secretory saccharides, bioaccumulation and directed flagella based shifting resulting out of hypo-doses of drug stimulation. Further, the prevalence of Enterobacteriaceae member strains has been witnessed producing Extended Spectrum β-Lactamases (ESBLs) and Carbapenemases. Drug resistance in viral entities has also posed challenge for public health programs. About 20% people die of viral hepatitis in one of Pakistan provinces. A counter malarial acrine drug is being tried against proteinaceous infectious particles (causing many transmissible neuro-diseases). These epigenetical agents have been a source of concern for our planet regarding food safety issues (e.g. infected meat). No doubt, man has made significant achievements in effective and neo-antimicrobials research, one wonders why not a single infectious agent has been completely knocked out. Our group has been focusing on ascertaining the basis of antibiotic deferring processes acquired by (indigenous) clinical strains. Accordingly, sub-lethal doses of the drug result in development of hyper-resistances. The bacteria have evolved the molecular genetical basis (and other parameters) for acquiring the resistance. For the containment and eradication of globally evolving MDR bacteria, it is crucial to understand and implement certain strategies/agents such as, probiotics, CRISPRs, bacteriophages, nanotechnology and phytochemicals.